Feb. 2024, Hokkaido University, Hokkaido University Presidential Commendation for Education and Research Excellence Award　　　　　　　　　　　　　　　

Feb. 2016, Hokkaido University, Hokkaido University Presidential Commendation for Education and Research Excellence Award　　　　　　　　　　　　　　　

Development of a PCR-dipstick DNA chromatography-based tool for the detection of CTX-M- and TEM-producing Escherichia coli and Klebsiella pneumoniae isolated from patients in Kafue and Katete districts of Zambia.
Misheck Shawa, Kyoko Hayashida, Naganori Nao, Atmika Paudel, Harvey Kamboyi, Herman Chambaro, Malala Mulavu, Cynthia Sipho Khumalo, Mike Nundwe, Tuvshinzaya Zorigt, Chinatsu Nakamura, Yongjin Qiu, Naoko Kawai, Maisa Kasanga, Joseph Chizimu, Lavel Moonga, Joseph Ndebe, Manyando Simbotwe, Shohei Ogata, Mulemba Samutela, Chie Nakajima, Roma Chilengi, Mable Mutengo, Masahiro Kajihara, Hirofumi Sawa, Bernard Hang'ombe, Yasuhiko Suzuki, Hideaki Higashi
BMC infectious diseases, 25, 1, 541, 541, 16 Apr. 2025, [International Magazine]
English, Scientific journal, In Zambia, 40% of clinical Gram-negative bacteria are either Escherichia coli or Klebsiella pneumoniae, with a high third-generation cephalosporin (3GC) resistance prevalence. Therefore, 3GC resistance surveillance is a crucial indicator for guiding focused intervention policies. However, the lack of genotypic diagnostic tools limits the ability to elucidate trends, especially in peri-urban and rural areas of developing countries. This study aimed to develop a rapid, cost-effective tool for the genotypic surveillance of 3GC resistance. Here, 900 stool samples collected from patients in Kafue (peri-urban, n = 400) and Katete (rural, n = 500) districts of Zambia were used for bacterial isolation on MacConkey agar supplemented with 1 μg/ml cefotaxime. Isolated 3GC-resistant strains were characterized by sequencing the 16S rRNA gene and screening for blaCTX-M and blaTEM genes using single polymerase chain reaction (PCR). Furthermore, selected 3GC-resistant strains were subjected to whole-genome sequencing (WGS) using MiSeq/HiSeq (n = 34) and MinION (n = 1). Using the data from this and other previous studies, we developed a rapid PCR-dipstick DNA chromatography-based tool for detecting blaCTX-M, blaTEM, E. coli-specific yaiO, and K. pneumoniae-specific khe genes. The prevalence of isolated 3GC resistant strains was 15.4% (139/900), dominated by E. coli (102/139, 73.4%). On PCR, the blaCTX-M gene was detected in 72.7% (101/139) of the isolates, while blaTEM was found in 46.8% (65/139) of the strains. The developed tool displayed a high level of agreement with WGS and single PCR/Sanger sequencing, with sensitivity and specificity ≥ 95% and Kappa ≥ 0.95 for each of the four target genes. We envisage that the simplicity and adaptability of this tool will be a significant advantage for the surveillance of 3GC resistance in Zambia and elsewhere.

Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants.
Yuki Anraku, Shunsuke Kita, Taishi Onodera, Akihiko Sato, Takashi Tadokoro, Shiori Ito, Yu Adachi, Ryutaro Kotaki, Tateki Suzuki, Jiei Sasaki, Nozomi Shiwa-Sudo, Naoko Iwata-Yoshikawa, Noriyo Nagata, Souta Kobayashi, Yasuhiro Kazuki, Mitsuo Oshimura, Takao Nomura, Michihito Sasaki, Yasuko Orba, Tadaki Suzuki, Hirofumi Sawa, Takao Hashiguchi, Hideo Fukuhara, Yoshimasa Takahashi, Katsumi Maenaka
Communications biology, 8, 1, 483, 483, 22 Mar. 2025, [International Magazine]
English, Scientific journal, Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and functional basis for the neutralizing activity of NT-108 has not yet been understood. Here, we demonstrated the therapeutic effects of NT-108 in a hamster model and its protective effects at low doses. Furthermore, we determined the cryo-EM structure of NT-108 in complex with SARS-CoV-2 spike. The single-chain Fv construction of NT-108 improved the cryo-EM maps because of the prevention of preferred orientations induced by Fab orientation. The footprints of NT-108 illuminated how escape mutations such as E484K evade from class 2 antibody recognition without ACE2 affinity attenuation. The functional and structural basis for the potent neutralizing activity of NT-108 provides insights into the rational design of therapeutic antibodies.

Malabaricone C isolated from edible plants as a potential inhibitor of SARS-CoV-2 infection.
Mutmainah, Yuta Murai, Ai Fujimoto, Rintaro Kawamura, Akira Kitamura, Sajeer Koolath, Seigo Usuki, Michihito Sasaki, Yasuko Orba, Yasuyuki Igarashi, Hirofumi Sawa, Akihiko Sato, Kenji Monde
Scientific reports, 15, 1, 8518, 8518, 12 Mar. 2025, [International Magazine]
English, Scientific journal, Although the SARS-CoV-2 epidemic worldwide has gradually decreased, in some areas, the situation has not yet been stamped and has become a global health emergency. It is quite possible that we could again be threatened by a new coronavirus. Therefore, new nucleotide analog drugs and vaccines or using drug repositioning for SARS-CoV-2 still has been developed, yet their safety and efficacy against COVID-19 remains underexplored. Malabaricone C is 2,6-dihydroxyphenyl acylphenol found in edible plants such as the mace spice of nutmeg derived from the seeds of Myristica fragrans. In this study, we identified malabaricone C as the first inhibitor of SARS-CoV-2 from natural food with a safe alternative for drugs. Malabaricone C and its chemical derivatives showed EC50 values of 1-1.5 μM against SARS-CoV-2 (WK-521, ancestral strain) and its variant strains in mammalian cells (HEK293T and Vero E6). In addition, we have successfully established novel evaluation system for the inhibition of SARS virus cell fusion by visualization for providing a versatile tool for study SARS-CoV-2 mediated fusion. Furthermore, our experiments suggested that malabaricone C could affect the distribution of sphingomyelin on the plasma membrane, which involves in viral infections. Thus, in light of the beneficial effect of malabaricone C on viral infection, the nontoxic malabaricone C is a suitable candidate as a drug that can be employed in the treatment and prevention of COVID-19. Moreover, it may potentially be used to treat acute infections of other enveloped viruses.

Functional dissection of the C-terminal domain of rabies virus RNA polymerase L protein.
Fumiki Izumi, Machiko Makino, Michihito Sasaki, Kento Nakagawa, Tatsuki Takahashi, Shoko Nishiyama, Yuji Fujii, Misuzu Okajima, Tatsunori Masatani, Manabu Igarashi, Hirofumi Sawa, Makoto Sugiyama, Naoto Ito
Journal of virology, e0208224, 11 Mar. 2025, [International Magazine]
English, Scientific journal, UNLABELLED: The rabies virus large (L) protein interacts with its cofactor phosphoprotein (P protein) to function as an RNA-dependent RNA polymerase (RdRp). The C-terminal domain (CTD) of the L protein plays a critical role in P protein binding. We previously reported that the highly conserved NPYNE sequence in the hydrophilic region of the CTD (positions 1929-1933 of the L protein [L1929-1933]) is important for both P protein binding and RdRp function. To elucidate the functional role of the CTD in detail, we examined the importance of each of the hydrophilic residues in the NPYNE sequence (underlined). A rabies virus mutant with Ala substitutions in these hydrophilic residues showed low replication capacity. Comprehensive analyses of a revertant of the mutant virus and a series of L protein mutants revealed that Asn at L1929 is crucial for both P protein binding and RdRp function. Analyses of the L protein mutants also showed that Asn at L1932 and Glu at L1933 have roles in RdRp function and P protein binding, respectively. Furthermore, we demonstrated that the NPYNE sequence is essential for stabilizing the L protein through the L-P interaction. In a previously determined L protein structure, all of the hydrophilic residues in the NPYNE sequence form the first α-helix in the CTD. Therefore, our findings indicate that this helix is important for P protein-binding ability, RdRp function, and stabilization of the L protein, thereby contributing to efficient viral replication. IMPORTANCE: Although RNA-dependent RNA polymerase of rhabdoviruses, which is composed of the large (L) protein and its cofactor phosphoprotein (P protein), has a high potential as a target for therapeutics against the viruses, the relationship between the structure and molecular functions is poorly understood. In this study, we functionally examined the C-terminal domain (CTD) of the rabies virus L protein as a model for the rhabdovirus L protein. We showed that the first α-helix in the CTD is important for the P protein-binding ability, RdRp function, and stability of the L protein. Since in the L-P complex structure, this helix does not form an interface with the P protein, we provide here the first evidence of an indirect contribution of the L protein CTD to the L-P interaction in rhabdoviruses. The findings in this study will be useful for developing therapeutics targeting the L-P interaction.

Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination.
Mizuki Fujisawa, Taishi Onodera, Daisuke Kuroda, Chidchamai Kewcharoenwong, Michihito Sasaki, Yukari Itakura, Kohei Yumoto, Arnone Nithichanon, Naoto Ito, Shinji Takeoka, Tadaki Suzuki, Hirofumi Sawa, Ganjana Lertmemongkolchai, Yoshimasa Takahashi
NPJ vaccines, 10, 1, 39, 39, 23 Feb. 2025, [International Magazine]
English, Scientific journal, Rabies vaccines require repeated immunization to robustly elicit neutralizing antibodies that prevent fatal diseases. Here, we analyzed rabies glycoprotein antibody repertoires at both polyclonal and monoclonal levels following repeated vaccination. Booster vaccination dramatically elevated the neutralizing activity of recalled antibodies, primarily targeting an immunodominant site III epitope with hydrophilic and rugged structures. Strikingly, the majority of site III-directed antibodies in the recall response used a convergent VH gene (IGHV3-30), and they exhibited more hydrophilic and shorter paratopes than non-site III antibodies, providing physicochemical advantages for binding to site III. Additionally, several amino acids on heavy chain CDR3 were identified as key sites for acquiring an ultrapotent neutralizing activity through site III binding. Our in-depth analysis of antibody repertoires revealed the molecular signatures of neutralizing antibodies generated by repeated rabies vaccination, possibly as a result of adaptive convergence.

First identification and whole genome characterization of rotavirus C in pigs in Zambia.
Hayato Harima, Yongjin Qiu, Michihito Sasaki, Joseph Ndebe, Kapila Penjaninge, Edgar Simulundu, Masahiro Kajihara, Aiko Ohnuma, Keita Matsuno, Naganori Nao, Yasuko Orba, Ayato Takada, Kanako Ishihara, William W Hall, Bernard M Hang'ombe, Hirofumi Sawa
Virology, 603, 110385, 110385, 31 Dec. 2024, [International Magazine]
English, Scientific journal, Rotavirus C (RVC) causes acute gastroenteritis in neonatal piglets. Despite the clinical importance of RVC infection, the distribution and prevalence in pig populations in most African countries remains unknown. In this study, we identified RVC in Zambian pigs by metagenomic analysis. The full genome sequence of the RVC revealed two different VP4 sequences, implying that two different RVC strains (ZP18-77-c1 and ZP18-77-c2) were present in the same sample. Genetic analyses demonstrated that all segments of ZP18-77-c1 and ZP18-77-c2 showed high nucleotide sequence identities (87.7-94.5%) to known porcine RVC strains, and ZP18-77-c1 and ZP18-77-c2 strains were assigned to genotype constellations, G1-P[4]/P[14]-I13-R5-C5-M1-A7-N9-T10-E5-H1. We further screened RVC genomes among pig feces collected in Zambia (n = 147) by RT-qPCR, and 78 samples (53.1%) were positive. This study demonstrated the first full genome sequence of African RVC strains with a relatively high prevalence of RVC infection in the pig populations in Zambia.

X-206 exhibits broad-spectrum anti-β-coronavirus activity, covering SARS-CoV-2 variants and drug-resistant isolates.
Jiei Sasaki, Akihiko Sato, Michihito Sasaki, Iori Okabe, Kota Kodama, Satoko Otsuguro, Kosuke Yasuda, Hirotatsu Kojima, Yasuko Orba, Hirofumi Sawa, Katsumi Maenaka, Yusuke Yanagi, Takao Hashiguchi
Antiviral research, 106039, 106039, 19 Nov. 2024, [International Magazine]
English, Scientific journal, Coronaviruses such as the Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2, causing MERS, SARS, and Coronavirus disease-19, respectively, are highly pathogenic to humans. Notably, several antiviral drugs against SARS-CoV-2, such as nirmatrelvir and remdesivir, have been approved. However, no approved vaccines or antiviral agents are available for other highly pathogenic β-coronaviruses. In this study, we identified two compounds, thapsigargin and X-206, that exhibit antiviral activities against SARS-CoV, MERS-CoV, and SARS-CoV-2. Notably, both compounds effectively inhibited the cell-to-cell fusion mediated by the Spike proteins of all three β-coronaviruses. X-206 exhibited antiviral activity against nirmatrelvir- and remdesivir-resistant SARS-CoV-2 isolates and SARS-CoV-2 variants, including Delta, BA.5, and XBB.1. Consequently, the mechanism of action of these compounds with anti-β-coronavirus activities may differ from that of the approved direct-acting drugs for SARS-CoV-2, thereby offering potential use as a cocktail with other antivirals, and serving as a chemical basis for developing therapeutic agents against β-coronaviruses in preparation for the next spillover and pandemic.

African lineage 1a West Nile virus isolated from crocodiles exhibits low neuroinvasiveness in mice.
Hiroko Kobayashi, Herman Chambaro, Koshiro Tabata, Takuma Ariizumi, Wallaya Phongphaew, Kunda Ndashe, Joseph Ndebe, Paul Fandamu, Shintaro Kobayashi, Naoto Ito, Michihito Sasaki, Bernard M Hang'ombe, Edgar Simulundu, Yasuko Orba, Hirofumi Sawa
The Journal of general virology, 105, 11, Nov. 2024, [International Magazine]
English, Scientific journal, West Nile virus (WNV) is a mosquito-borne flavivirus that causes encephalitis in humans and infects crocodiles, resulting in rashes and neurological signs. In Zambia, two distinct lineages of WNV have been detected in neighbouring areas: lineage 2 in mosquitoes and lineage 1a in farmed crocodiles. Considering the risk of direct or vector-mediated WNV transmission from crocodiles to mammals, it is necessary to elucidate the pathogenicity of WNV strains derived from crocodiles. In this study, WNV was successfully isolated from naturally infected farmed crocodiles (Croc110/2019/1/ZM, Croc110). We then investigated its proliferation and pathogenicity in mice in comparison with a WNV isolate from mosquitoes in Zambia (Zmq16) and two reference strains, including one highly pathogenic (NY99) and one low pathogenic (Eg101) strain. Although viral proliferation in Vero and mammalian neuronal cells was comparable among the strains, Croc110 exhibited low cell-to-cell transmission efficiency. In vivo, more than 70% of mice (C57BL/6) intracerebrally inoculated with Croc110 displayed neurological signs, and Croc110-infected mice exhibited similarly high mortality rates as NY99- and Zmq16-infected mice. Meanwhile, comparable virus growth was observed among the strains in the brain. However, the virulence of Croc110 was significantly lower than that of Zmq16 and NY99 following intradermal (ID) and intraperitoneal inoculation. Consistently, Croc110 displayed lower growth than Zmq16 and NY99 in the brain and peripheral tissues after ID inoculation. Our study revealed that the crocodile-derived WNV strain is less neuroinvasive in mice, and it exhibits distinct pathogenicity from the highly pathogenic mosquito-derived WNV strain circulating in Zambia.

A first report of rotavirus B from Zambian pigs leading to the discovery of a novel VP4 genotype P[9].
Hayato Harima, Yongjin Qiu, Michihito Sasaki, Joseph Ndebe, Kapila Penjaninge, Edgar Simulundu, Masahiro Kajihara, Aiko Ohnuma, Keita Matsuno, Naganori Nao, Yasuko Orba, Ayato Takada, Kanako Ishihara, William W Hall, Bernard M Hang'ombe, Hirofumi Sawa
Virology journal, 21, 1, 263, 263, 24 Oct. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Rotavirus B (RVB) causes diarrhea in humans and pigs. Although various RVB strains were identified in humans and various animals globally, little is known about the epidemiology RVB infection in Africa. In this study, we attempted to examine the prevalence of RVB infection in pig populations in Zambia. METHODS: Metagenomic analyses were conducted on pig feces collected in Zambia to detect double stranded RNA viruses, including RVB. To clarify the prevalence of RVB infection in pig populations in Zambia, 147 fecal samples were screened for the RVB detection by RT-qPCR. Full genome sequence of a detected RVB was determined by Sanger sequencing and genetically analyzed. RESULTS: The metagenomic analyses revealed that RVB sequence reads and contigs of RVB were detected from one fecal sample collected from pigs in Zambia. RT-qPCR screening detected RVB genomes in 36.7% (54/147) of fecal samples. Among 54 positive samples, 13 were positive in non-diarrheal samples (n = 48, 27.1%) and 41 in diarrheal samples (n = 99, 41.4%). Genetic analyses demonstrated that all the segments of ZP18-18, except for VP4, had high nucleotide sequence identities (80.6-92.6%) with all other known RVB strains detected in pigs. In contrast, the VP4 sequence of ZP18-18 was highly divergent from other RVB strains (< 64.6% identities) and formed a distinct lineage in the phylogenetic tree. Notably, the VP8 subunit of the VP4 showed remarkably low amino acid identities (33.3%) to those of known RVB strains, indicating that the VP8 subunit of ZP18-18 was unique among RVB strains. According to the whole genome classification for RVB, ZP18-18 was assigned to a genotype constellation, G18-P[9]-I12-R4-C4-M4-A8-N10-T5-E4-H7 with the newly established VP4 genotype P[9]. CONCLUSIONS: This current study updates the geographical distribution and the genetic diversity of RVB. Given the lack of information regarding RVB in Africa, further RVB surveillance is required to assess the potential risk to humans and animals.

Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1
Hisano Yajima, Yuki Anraku, Yu Kaku, Kanako Terakado Kimura, Arnon Plianchaisuk, Kaho Okumura, Yoshiko Nakada-Nakura, Yusuke Atarashi, Takuya Hemmi, Daisuke Kuroda, Yoshimasa Takahashi, Shunsuke Kita, Jiei Sasaki, Hiromi Sumita, Keita Matsuno, Naganori Nao, Hirofumi Sawa, Keita Mizuma, Jingshu Li, Izumi Kida, Yume Mimura, Yuma Ohari, Shinya Tanaka, Masumi Tsuda, Lei Wang, Yoshikata Oda, Zannatul Ferdous, Kenji Shishido, Hiromi Mohri, Miki Iida, Takasuke Fukuhara, Tomokazu Tamura, Rigel Suzuki, Saori Suzuki, Shuhei Tsujino, Hayato Ito, Naoko Misawa, Ziyi Guo, Alfredo A. Hinay, Kaoru Usui, Wilaiporn Saikruang, Spyridon Lytras, Keiya Uriu, Ryo Yoshimura, Shusuke Kawakubo, Luca Nishumura, Yusuke Kosugi, Shigeru Fujita, Jarel Elgin M.Tolentino, Luo Chen, Lin Pan, Wenye Li, Maximilian Stanley Yo, Kio Horinaka, Mai Suganami, Mika Chiba, Kyoko Yasuda, Keiko Iida, Adam Patrick Strange, Naomi Ohsumi, Shiho Tanaka, Eiko Ogawa, Tsuki Fukuda, Rina Osujo, Kazuhisa Yoshimura, Kenji Sadamas, Mami Nagashima, Hiroyuki Asakura, Isao Yoshida, So Nakagawa, Kazuo Takayama, Rina Hashimoto, Sayaka Deguchi, Yukio Watanabe, Yoshitaka Nakata, Hiroki Futatsusako, Ayaka Sakamoto, Naoko Yasuhara, Tateki Suzuki, Yukari Nakajima, Takashi Irie, Ryoko Kawabata, Kaori Sasaki-Tabata, Terumasa Ikeda, Hesham Nasser, Ryo Shimizu, M. S. T. Monira Begum, Michael Jonathan, Yuka Mugita, Sharee Leong, Otowa Takahashi, Takamasa Ueno, Chihiro Motozono, Mako Toyoda, Akatsuki Saito, Anon Kosaka, Miki Kawano, Natsumi Matsubara, Tomoko Nishiuchi, Jiri Zahradnik, Prokopios Andrikopoulos, Miguel Padilla-Blanco, Aditi Konar, Jumpei Ito, Katsumi Maenaka, Kei Sato, Takao Hashiguchi
Nature Communications, 15, 1, Springer Science and Business Media LLC, 07 Oct. 2024
Scientific journal

Characterization of a mammalian orthoreovirus isolated from the large flying fox, Pteropus vampyrus, in Indonesia.
Kittiya Intaruck, Koshiro Tabata, Yukari Itakura, Nijiho Kawaguchi, Mai Kishimoto, Agus Setiyono, Ekowati Handharyani, Hayato Harima, Takashi Kimura, William W Hall, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
The Journal of general virology, 105, 9, Sep. 2024, [International Magazine]
English, Scientific journal, Fruit bats serve as an important reservoir for many zoonotic pathogens, including Nipah virus, Hendra virus, Marburg virus and Lyssavirus. To gain a deeper insight into the virological characteristics, pathogenicity and zoonotic potential of bat-borne viruses, recovery of infectious viruses from field samples is important. Here, we report the isolation and characterization of a mammalian orthoreovirus (MRV) from a large flying fox (Pteropus vampyrus) in Indonesia, which is the first detection of MRV in Southeast Asia. MRV was recovered from faecal samples of three different P. vampyrus in Central Java. Nucleotide sequence analysis revealed that the genome of the three MRV isolates shared more than 99% nucleotide sequence identity. We tentatively named one isolated strain as MRV12-52 for further analysis and characterization. Among 10 genome segments, MRV12-52 S1 and S4, which encode the cell-attachment protein and outer capsid protein, had 93.6 and 95.1% nucleotide sequence identities with known MRV strains, respectively. Meanwhile, the remaining genome segments of MRV12-52 were divergent with 72.9-80.7 % nucleotide sequence identities. Based on the nucleotide sequence of the S1 segment, MRV12-52 was grouped into serotype 2, and phylogenetic analysis demonstrated evidence of past reassortment events. In vitro characterization of MRV12-52 showed that the virus efficiently replicated in BHK-21, HEK293T and A549 cells. In addition, experimental infection of laboratory mice with MRV12-52 caused severe pneumonia with 75% mortality. This study highlights the presence of pathogenic MRV in Indonesia, which could serve as a potential animal and public health concern.

β-d-N4-hydroxycytidine, a metabolite of molnupiravir, exhibits in vitro antiviral activity against rabies virus.
Kei Konishi, Shinji Kusakabe, Nijiho Kawaguchi, Takao Shishido, Naoto Ito, Michiko Harada, Satoshi Inoue, Ken Maeda, William W Hall, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki, Akihiko Sato
Antiviral research, 229, 105977, 105977, Sep. 2024, [International Magazine]
English, Scientific journal, Rabies is a fatal neurological disorder caused by rabies virus (RABV) infection. Approximately 60,000 patients die from rabies annually, and there are no effective treatments for this disease. Nucleoside analogs are employed as antiviral drugs based on their broad antiviral spectrum, and certain nucleoside analogs have been reported to exhibit anti-RABV activity. The nucleoside analog β-d-N4-hydroxycytidine (NHC) has antiviral effects against a range of RNA viruses. Molnupiravir (MPV), a prodrug of NHC, is clinically used as an oral antiviral drug for coronavirus infections. Despite its broad-spectrum activity, the antiviral activity of NHC against RABV remains unclear. In this study, we reveal that NHC exhibits comparable in vitro anti-RABV activity as ribavirin and favipiravir (also known as T-705) with a 90% effective concentration of 6 μM in mouse neuroblastoma cells. NHC reduced viral loads in neuronal and nonneuronal cells in a dose-dependent manner. Both laboratory and field RABVs (fixed and street strains, respectively) were susceptible to NHC. However, no increase in survival or reduction in viral titers in the brain was observed in RABV-infected mice treated prophylactically with MPV. These findings highlight the potential and challenges of NHC in the treatment of RABV infection.

Increased production of orthoflavivirus single-round infectious particles produced in mammalian cells at a suboptimal culture temperature of 28°C
Koshiro Tabata, Shintaro Kobayashi, Yukari Itakura, Gabriel Gonzalez, Chilekwa F. Kabamba, Shinji Saito, Michihito Sasaki, William W. Hall, Hirofumi Sawa, Yasuko Orba
Journal of Virological Methods, 329, 115007, 115007, Elsevier BV, Sep. 2024
Scientific journal

Reverse genetic approaches allowing the characterization of the rabies virus street strain belonging to the SEA4 subclade.
Nijiho Kawaguchi, Yukari Itakura, Kittiya Intaruck, Takuma Ariizumi, Michiko Harada, Satoshi Inoue, Ken Maeda, Naoto Ito, William W Hall, Hirofumi Sawa, Yasuko Orba, Michihito Sasaki
Scientific reports, 14, 1, 18509, 18509, 09 Aug. 2024, [International Magazine]
English, Scientific journal, Rabies virus (RABV) is the causative agent of rabies, a lethal neurological disease in mammals. RABV strains can be classified into fixed strains (laboratory strains) and street strains (field/clinical strains), which have different properties including cell tropism and neuroinvasiveness. RABV Toyohashi strain is a street strain isolated in Japan from an imported case which had been bitten by rabid dog in the Philippines. In order to facilitate molecular studies of RABV, we established a reverse genetics (RG) system for the study of the Toyohashi strain. The recombinant virus was obtained from a cDNA clone of Toyohashi strain and exhibited similar growth efficiency as the original virus in cultured cell lines. Both the original and recombinant strains showed similar pathogenicity with high neuroinvasiveness in mice, and the infected mice developed a long and inconsistent incubation period, which is characteristic of street strains. We also generated a recombinant Toyohashi strain expressing viral phosphoprotein (P protein) fused with the fluorescent protein mCherry, and tracked the intracellular dynamics of the viral P protein using live-cell imaging. The presented reverse genetics system for Toyohashi strain will be a useful tool to explore the fundamental molecular mechanisms of the replication of RABV street strains.

A wide distribution of Beiji nairoviruses and related viruses in Ixodes ticks in Japan.
Mai Kishimoto, Yukari Itakura, Koshiro Tabata, Rika Komagome, Hiroki Yamaguchi, Kohei Ogasawara, Ryo Nakao, Yongjin Qiu, Kozue Sato, Hiroki Kawabata, Masahiro Kajihara, Naota Monma, Junji Seto, Asako Shigeno, Masayuki Horie, Michihito Sasaki, William W Hall, Hirofumi Sawa, Yasuko Orba, Keita Matsuno
Ticks and tick-borne diseases, 15, 6, 102380, 102380, 11 Jul. 2024, [International Magazine]
English, Scientific journal, Beiji nairovirus (BJNV), in the family Nairoviridae, the order Bunyavirales, was recently reported as a causative agent of an emerging tick-borne zoonotic infection in China. This study investigated the prevalence of BJNV in ticks in Japan. Screening of over 2,000 ticks from multiple regions revealed a widespread distribution of BJNV and BJNV-related viruses in Japan, particularly in the northern island, and in other high altitude areas with exclusive occurrence of Ixodes ticks. Phylogenetic analysis identified three distinct groups of nairoviruses in ticks in Japan: BJNV, Yichun nairovirus (YCNV) and a newly identified Mikuni nairovirus (MKNV). BJNV and YCNV variants identified in ticks in Japan exhibited high nucleotide sequence identities to those in China and Russia with evidence of non-monophyletic evolution among BJNVs, suggesting multiple cross-border transmission events of BJNV between the Eurasian continent and Japan. Whole genome sequencing of BJNV and MKNV revealed a unique GA-rich region in the S segment, the significance of which remains to be determined. In conclusion, the present study has shown a wide distribution and diversity of BJNV-related nairoviruses in Ixodes ticks in Japan and has identified unique genomic structures. The findings demonstrate the significance of BJNV as well as related viruses in Japan and highlight the necessity of monitoring emerging nairovirus infections and their potential risks to public health.

Detection of Human Adenovirus and Rotavirus in Wastewater in Lusaka, Zambia: Demonstrating the Utility of Environmental Surveillance for the Community
Ngonda Saasa, Ethel M’kandawire, Joseph Ndebe, Mulenga Mwenda, Fred Chimpukutu, Andrew Nalishuwa Mukubesa, Fred Njobvu, Doreen Mainza Shempela, Jay Sikalima, Carol Chiyesu, Bruce Muvwanga, Sarah M. Nampokolwe, Clement Sulwe, Thokozile Khondiwa, Todd Jennings, Ameck Kamanga, Edgar Simulundu, Conceptor Mulube, Wizaso Mwasinga, Jalaimo Mumeka, John Simwanza, Patrick Sakubita, Otridah Kapona, Chilufya Susan Aneta Mulenga, Musole Chipoya, Kunda Musonda, Nathan Kapata, Nyambe Sinyange, Muzala Kapina, Joyce Siwila, Misheck Shawa, Masahiro Kajihara, Ayato Takada, Hirofumi Sawa, Simulyamana A. Choonga, Roma Chilengi, Earnest Muyunda, King S. Nalubamba, Bernard M. Hang’ombe
Pathogens, 13, 6, 486, 486, MDPI AG, 07 Jun. 2024
Scientific journal, Enteric infections due to viral pathogens are a major public health concern. Detecting the risk areas requires a strong surveillance system for pathogenic viruses in sources such as wastewater. Towards building an environmental surveillance system in Zambia, we aimed to identify group A rotavirus (RVA) and human adenovirus (HAdV) in wastewater. Convenient sampling was conducted at four study sites every Tuesday for five consecutive weeks. The research team focused on three different methods of viral concentration to determine the suitability in terms of cost and applicability for a regular surveillance system: the bag-mediated filtration system (BMFS), polyethylene glycol-based (PEG) precipitation, and skimmed milk (SM) flocculation. We screened 20 wastewater samples for HAdV and RVA using quantitative polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR). Of the 20 samples tested using qPCR, 18/20 (90%) tested positive for HAdV and 14/20 (70%) tested positive for RVA. For the genetic sequencing, qPCR positives were subjected to cPCR, of which 12 positives were successfully amplified. The human adenovirus was identified with a nucleotide identity range of 98.48% to 99.53% compared with the reference genome from GenBank. The BMFS and SM flocculation were the most consistent viral concentration methods for HAdV and RVA, respectively. A statistical analysis of the positives showed that viral positivity differed by site (p < 0.001). SM and PEG may be the most appropriate options in resource-limited settings such as Zambia due to the lower costs associated with these concentration methods. The demonstration of HAdV and RVA detection in wastewater suggests the presence of the pathogens in the communities under study and the need to establish a routine wastewater surveillance system for the identification of pathogens.

Antimicrobial Use Survey and Detection of ESBL-Escherichia coli in Commercial and Medium-/Small-Scale Poultry Farms in Selected Districts of Zambia
Taona Sinyawa, Misheck Shawa, Geoffrey M. Muuka, Fusya Goma, Paul Fandamu, Joseph Yamweka Chizimu, Cynthia Sipho Khumalo, Malala Mulavu, Masuzyo Ngoma, Herman Moses Chambaro, Harvey Kakoma Kamboyi, Masahiro Kajihara, Hirofumi Sawa, Yasuhiko Suzuki, Hideaki Higashi, Geoffrey Mainda, Musso Munyeme, John Bwalya Muma, Christian Owusu Nyantakyi, Beverly Egyir, Bernard Mudenda Hang’ombe
Antibiotics, 13, 5, 467, 467, MDPI AG, 20 May 2024
Scientific journal, Antimicrobial resistance (AMR) among Escherichia coli from food animals is a rising problem, and heavy antimicrobial use in poultry is a contributing factor. In Zambia, studies linking poultry-associated AMR and antibiotic use (AMU) are rare. This study aimed to investigate commercial and medium-/small-scale poultry farmers’ usage of antimicrobials based on a questionnaire survey in ten districts of Zambia. In addition, the study characterized extended-spectrum β-lactamase (ESBL)-producing E. coli isolates obtained from poultry in the same districts. Data regarding knowledge and usage of antimicrobials were collected from commercial and medium-/small-scale poultry farmers using a pre-tested structured questionnaire. At the same time, cloacal samples were collected and analyzed. One hundred and fifty E. coli isolates were tested for antimicrobial susceptibility using eight antibiotic classes. The isolates were further screened for ESBL production by streaking them on cefotaxime (CTX)-supplemented MacConkey agar, then subjecting them to sequencing on a NextSeq. The questionnaire survey showed that more medium-/small-scale than commercial poultry farmers used antimicrobials (OR = 7.70, 95% CI = 2.88–20.61) but less prescriptions (OR = 0.02, 95% CI = 0.00–0.08). Susceptibility testing revealed that resistance was highest to ampicillin (128/148, 86.5%) and tetracycline (101/136, 74.3%) and that the prevalence of multidrug resistance (MDR) (28/30, 93.3%) was high. Whole-genome sequencing (WGS) of eight (8/30, 26.7%) isolates with CTX Minimum Inhibitory Concentration (MIC) ≥ 4 µg/mL revealed the presence of ESBL-encoding genes blaCTX-M-14, blaCTX-M-55, and blaTEM. WGS also detected other AMR genes for quinolones, aminoglycosides, phenicols, tetracycline, macrolides, and folate-pathway antagonists. Altogether, the questionnaire survey results showed a higher proportion of AMU and lower prescription usage among medium-/small-scale farmers. In addition, our results emphasize the circulation of ESBL-producing E. coli strains with associated MDR. It is critical to educate farmers about AMR risks and to encourage responsible usage of antimicrobials. Furthermore, there is a need to strengthen regulations limiting access to antimicrobials. Finally, there is a need to establish a one health system to guide public health response.

Rab27a promotes degradation of West Nile virus E protein in the lysosome.
Shintaro Kobayashi, Seira Kawai, Yukine Fukuda, Haruto Eguchi, Keisuke Maezono, Passawat Thammahakin, Hirofumi Sawa, Hiroaki Kariwa
iScience, 27, 4, 109539, 109539, 19 Apr. 2024, [International Magazine]
English, Scientific journal, Rab27a, a Rab family small GTPases, plays an important role in the trafficking and secretion of the intracellular proteins and has been reported to promote various viral multiplication. However, whether Rab27a is involved in West Nile virus (WNV) multiplication is unknown. This study examined the ability of Rab27a to suppress WNV multiplication. The inhibition of Rab27a expression increased viral multiplication and the intracellular levels of WNV structural proteins, E and prM proteins. Rab27a partially colocalized with E protein, mainly in the perinuclear region, while inhibition of Rab27a expression resulted in diffuse subcellular localization of E protein. In addition, some of the perinuclear E protein colocalized with the lysosomal marker LAMP1, and inhibition of lysosomal acidification increased intracellular levels of Rab27a and E proteins. These observations suggested that Rab27a inhibits WNV multiplication by inducing the degradation of viral protein in lysosomes.

Genes involved in the limited spread of SARS-CoV-2 in the lower respiratory airways of hamsters may be associated with adaptive evolution.
Kosuke Takada, Yasuko Orba, Yurie Kida, Jiaqi Wu, Chikako Ono, Yoshiharu Matsuura, So Nakagawa, Hirofumi Sawa, Tokiko Watanabe
Journal of virology, e0178423, 16 Apr. 2024, [International Magazine]
English, Scientific journal, Novel respiratory viruses can cause a pandemic and then evolve to coexist with humans. The Omicron strain of severe acute respiratory syndrome coronavirus 2 has spread worldwide since its emergence in late 2021, and its sub-lineages are now established in human society. Compared to previous strains, Omicron is markedly less invasive in the lungs and causes less severe disease. One reason for this is that humans are acquiring immunity through previous infection and vaccination, but the nature of the virus itself is also changing. Using our newly established low-volume inoculation system, which reflects natural human infection, we show that the Omicron strain spreads less efficiently into the lungs of hamsters compared with an earlier Wuhan strain. Furthermore, by characterizing chimeric viruses with the Omicron gene in the Wuhan strain genetic background and vice versa, we found that viral genes downstream of ORF3a, but not the S gene, were responsible for the limited spread of the Omicron strain in the lower airways of the virus-infected hamsters. Moreover, molecular evolutionary analysis of SARS-CoV-2 revealed a positive selection of genes downstream of ORF3a (M and E genes). Our findings provide insight into the adaptive evolution of the virus in humans during the pandemic convergence phase.IMPORTANCEThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread worldwide since its emergence in late 2021, and its sub-lineages are established in human society. Compared to previous strains, the Omicron strain is less invasive in the lower respiratory tract, including the lungs, and causes less severe disease; however, the mechanistic basis for its restricted replication in the lower airways is poorly understood. In this study, using a newly established low-volume inoculation system that reflects natural human infection, we demonstrated that the Omicron strain spreads less efficiently into the lungs of hamsters compared with an earlier Wuhan strain and found that viral genes downstream of ORF3a are responsible for replication restriction in the lower respiratory tract of Omicron-infected hamsters. Furthermore, we detected a positive selection of genes downstream of ORF3a (especially the M and E genes) in SARS-CoV-2, suggesting that these genes may undergo adaptive changes in humans.

Combinatorial Approach with Mass Spectrometry and Lectin Microarray Dissected Site-Specific Glycostem and Glycoleaf Features of the Virion-Derived Spike Protein of Ancestral and γ Variant SARS-CoV-2 Strains.
Takahiro Hiono, Hiroaki Sakaue, Azusa Tomioka, Hiroyuki Kaji, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Atsushi Kuno
Journal of proteome research, 23, 4, 1408, 1419, 05 Apr. 2024, [International Magazine]
English, Scientific journal, The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted public health globally. As the glycosylation of viral envelope glycoproteins is strongly associated with their immunogenicity, intensive studies have been conducted on the glycans of the glycoprotein of SARS-CoV-2, the spike (S) protein. Here, we conducted intensive glycoproteomic analyses of the SARS-CoV-2 S protein of ancestral and γ-variant strains using a combinatorial approach with two different technologies: mass spectrometry (MS) and lectin microarrays (LMA). Our unique MS1-based glycoproteomic technique, Glyco-RIDGE, in addition to MS2-based Byonic search, identified 1448 (ancestral strain) and 1785 (γ-variant strain) site-specific glycan compositions, respectively. Asparagine at amino acid position 20 (N20) is mainly glycosylated within two successive potential glycosylation sites, N17 and N20, of the γ-variant S protein; however, we found low-frequency glycosylation at N17. Our novel approaches, glycostem mapping and glycoleaf scoring, also illustrate the moderately branched/extended, highly fucosylated, and less sialylated natures of the glycoforms of S proteins. Subsequent LMA analysis emphasized the intensive end-capping of glycans by Lewis fucoses, which complemented the glycoproteomic features. These results illustrate the high-resolution glycoproteomic features of the SARS-CoV-2 S protein, contributing to vaccine design and understanding of viral protein synthesis.

Detection of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacteriaceae from Diseased Broiler Chickens in Lusaka District, Zambia.
Chikwanda Chileshe, Misheck Shawa, Nelson Phiri, Joseph Ndebe, Cynthia Sipho Khumalo, Chie Nakajima, Masahiro Kajihara, Hideaki Higashi, Hirofumi Sawa, Yasuhiko Suzuki, Walter Muleya, Bernard Mudenda Hang'ombe
Antibiotics (Basel, Switzerland), 13, 3, 15 Mar. 2024, [International Magazine]
English, Scientific journal, Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has resulted in non-prudent antimicrobial use on farms, intending to prevent and treat poultry diseases for growth optimisation and maximising profits. This cross-sectional study aimed to identify the different types of bacteria causing diseases in chickens in Lusaka and to detect the extended-spectrum lactamase (ESBL)-encoding genes. We collected 215 samples from 91 diseased chickens at three post-mortem facilities and screened them for Gram-negative bacteria. Of these samples, 103 tested positive for various clinically relevant Enterobacteriaceae, including Enterobacter (43/103, 41.7%), Escherichia coli (20/103, 19.4%), Salmonella (10/103, 9.7%), and Shigella (8/103, 7.8%). Other isolated bacteria included Yersinia, Morganella, Proteus, and Klebsiella, which accounted for 21.4%. E. coli, Enterobacter, Salmonella, and Shigella were subjected to antimicrobial susceptibility testing. The results revealed that E. coli, Enterobacter, and Shigella were highly resistant to tetracycline, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole, while Salmonella showed complete susceptibility to all tested antibiotics. The observed resistance patterns correlated with antimicrobial usage estimated from sales data from a large-scale wholesale and retail company. Six (6/14, 42.9%) E. coli isolates tested positive for blaCTX-M, whilst eight (8/14, 57.1%) Enterobacter samples tested positive for blaTEM. Interestingly, four (4/6, 66.7%) of the E. coli isolates carrying blaCTX-M-positive strains were also positive for blaTEM. Sanger sequencing of the PCR products revealed that five (5/6, 83.3%) of the abovementioned isolates possessed the blaCTX-M-15 allele. The results suggest the presence of potentially pathogenic ESBL-producing Enterobacteriaceae in poultry, threatening public health.

Establishment of a lethal mouse model of emerging tick-borne orthonairovirus infections.
Takuma Ariizumi, Koshiro Tabata, Yukari Itakura, Hiroko Kobayashi, William W Hall, Michihito Sasaki, Hirofumi Sawa, Keita Matsuno, Yasuko Orba
PLoS pathogens, 20, 3, e1012101, Mar. 2024, [International Magazine]
English, Scientific journal, Emerging and reemerging tick-borne virus infections caused by orthonairoviruses (family Nairoviridae), which are genetically distinct from Crimean-Congo hemorrhagic fever virus, have been recently reported in East Asia. Here, we have established a mouse infection model using type-I/II interferon receptor-knockout mice (AG129 mice) both for a better understanding of the pathogenesis of these infections and validation of antiviral agents using Yezo virus (YEZV), a novel orthonairovirus causing febrile illnesses associated with tick bites in Japan and China. YEZV-inoculated AG129 mice developed hepatitis with body weight loss and died by 6 days post infection. Blood biochemistry tests showed elevated liver enzyme levels, similar to YEZV-infected human patients. AG129 mice treated with favipiravir survived lethal YEZV infection, demonstrating the anti-YEZV effect of this drug. The present mouse model will help us better understand the pathogenicity of the emerging tick-borne orthonairoviruses and the development of specific antiviral agents for their treatment.

Immunogenicity and protective efficacy of a co-formulated two-in-one inactivated whole virus particle COVID-19/influenza vaccine.
Chimuka Handabile, Marumi Ohno, Toshiki Sekiya, Naoki Nomura, Tomomi Kawakita, Mamiko Kawahara, Masafumi Endo, Tomohiro Nishimura, Minako Okumura, Shinsuke Toba, Michihito Sasaki, Yasuko Orba, Brendon Y Chua, Louise C Rowntree, Thi H O Nguyen, Masashi Shingai, Akihiko Sato, Hirofumi Sawa, Kazumasa Ogasawara, Katherine Kedzierska, Hiroshi Kida
Scientific reports, 14, 1, 4204, 4204, 20 Feb. 2024, [International Magazine]
English, Scientific journal, Due to the synchronous circulation of seasonal influenza viruses and severe acute respiratory coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19), there is need for routine vaccination for both COVID-19 and influenza to reduce disease severity. Here, we prepared individual WPVs composed of formalin-inactivated SARS-CoV-2 WK 521 (Ancestral strain; Co WPV) or influenza virus [A/California/07/2009 (X-179A) (H1N1) pdm; Flu WPV] to produce a two-in-one Co/Flu WPV. Serum analysis from vaccinated mice revealed that a single dose of Co/Flu WPV induced antigen-specific neutralizing antibodies against both viruses, similar to those induced by either type of WPV alone. Following infection with either virus, mice vaccinated with Co/Flu WPV showed no weight loss, reduced pneumonia and viral titers in the lung, and lower gene expression of proinflammatory cytokines, as observed with individual WPV-vaccinated. Furthermore, a pentavalent vaccine (Co/qFlu WPV) comprising of Co WPV and quadrivalent influenza vaccine (qFlu WPV) was immunogenic and protected animals from severe COVID-19. These results suggest that a single dose of the two-in-one WPV provides efficient protection against SARS-CoV-2 and influenza virus infections with no evidence of vaccine interference in mice. We propose that concomitant vaccination with the two-in-one WPV can be useful for controlling both diseases.

Phylogenetic Analysis of Newcastle Disease Virus Isolated from Poultry in Live Bird Markets and Wild Waterfowl in Zambia.
Annie Kalonda, Ngonda Saasa, Masahiro Kajihara, Naganori Nao, Ladslav Moonga, Joseph Ndebe, Akina Mori-Kajihara, Andrew Nalishuwa Mukubesa, Yoshihiro Sakoda, Hirofumi Sawa, Ayato Takada, Edgar Simulundu
Microorganisms, 12, 2, 08 Feb. 2024, [International Magazine]
English, Scientific journal, Poultry production is essential to the economy and livelihood of many rural Zambian households. However, the industry is threatened by infectious diseases, particularly Newcastle disease virus (NDV) infection. Therefore, this study employed next-generation sequencing to characterise six NDV isolates from poultry in Zambia's live bird markets (LBMs) and wild waterfowl. Four NDV isolates were detected from 410 faecal samples collected from chickens in LBMs in Lusaka and two from 2851 wild birds from Lochinvar National Park. Phylogenetic analysis revealed that the four NDVs from LBM clustered in genotype VII and sub-genotype VII.2 were closely related to viruses previously isolated in Zambia and other Southern African countries, suggesting possible local and regional transboundary circulation of the virus. In contrast, the two isolates from wild birds belonged to class I viruses, genotype 1, and were closely related to isolates from Europe and Asia, suggesting the possible introduction of these viruses from Eurasia, likely through wild bird migration. The fusion gene cleavage site motif for all LBM-associated isolates was 112RRQKR|F117, indicating that the viruses are virulent, while the isolates from wild waterfowl had the typical 112ERQER|L117 avirulent motif. This study demonstrates the circulation of virulent NDV strains in LBMs and has, for the first time, characterised NDV from wild birds in Zambia. The study further provides the first whole genomes of NDV sub-genotype VII.2 and genotype 1 from Zambia and stresses the importance of surveillance and molecular analysis for monitoring the circulation of NDV genotypes and viral evolution.

血管内皮細胞におけるSARS-CoV-2侵入機構の解析(Analysis of SARS-CoV-2 uptake mechanism in vascular endothelial cells)　　　　　　　　　　　　　　　
桜井 優弥, 間石 奈湖, 藤岡 容一郎, 大場 雄介, 武田 遼, 佐々木 道仁, 大場 靖子, 樋田 泰浩, 澤 洋文, 樋田 京子
日本病理学会会誌, 113, 1, 369, 369, (一社)日本病理学会, Feb. 2024
English

Trends, patterns and relationship of antimicrobial use and resistance in bacterial isolates tested between 2015-2020 in a national referral hospital of Zambia.
Misheck Shawa, Atmika Paudel, Herman Chambaro, Harvey Kamboyi, Ruth Nakazwe, Luke Alutuli, Tuvshinzaya Zorigt, Taona Sinyawa, Mulemba Samutela, Joseph Chizimu, Manyando Simbotwe, Kyoko Hayashida, Naganori Nao, Masahiro Kajihara, Yoshikazu Furuta, Yasuhiko Suzuki, Hirofumi Sawa, Bernard Hang'ombe, Hideaki Higashi
PloS one, 19, 4, e0302053, 2024, [International Magazine]
English, Scientific journal, Increased antimicrobial resistance (AMR) among bacteria underscores the need to strengthen AMR surveillance and promote data-based prescribing. To evaluate trends and associations between antimicrobial usage (AMU) and AMR, we explored a dataset of 34,672 bacterial isolates collected between 2015 and 2020 from clinical samples at the University Teaching Hospital (UTH) in Lusaka, Zambia. The most frequently isolated species were Escherichia coli (4,986/34,672; 14.4%), Staphylococcus aureus (3,941/34,672; 11.4%), and Klebsiella pneumoniae (3,796/34,672; 10.9%). Of the 16 drugs (eight classes) tested, only amikacin and imipenem showed good (> 50%) antimicrobial activity against both E. coli and K. pneumoniae, while nitrofurantoin was effective only in E. coli. Furthermore, 38.8% (1,934/4,980) of E. coli and 52.4% (2,079/3,791) of K. pneumoniae isolates displayed multidrug resistance (MDR) patterns on antimicrobial susceptibility tests. Among S. aureus isolates, 44.6% (973/2,181) were classified as methicillin-resistant (MRSA). Notably, all the MRSA exhibited MDR patterns. The annual hospital AMR rates varied over time, while there was a weak positive relationship (r = 0.38, 95% CI = 0.11-0.60) between the monthly use of third-generation cephalosporins (3GCs) and 3GC resistance among Enterobacterales. Overall, the results revealed high AMR rates that fluctuated over time, with a weak positive relationship between 3GC use and resistance. To our knowledge, this is the first report to evaluate the association between AMU and AMR in Zambia. Our results highlight the need to strengthen antimicrobial stewardship programs and optimize AMU in hospital settings.

Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model.
Michihito Sasaki, Tatsuki Sugi, Shun Iida, Yuichiro Hirata, Shinji Kusakabe, Kei Konishi, Yukari Itakura, Koshiro Tabata, Mai Kishimoto, Hiroko Kobayashi, Takuma Ariizumi, Kittiya Intaruck, Haruaki Nobori, Shinsuke Toba, Akihiko Sato, Keita Matsuno, Junya Yamagishi, Tadaki Suzuki, William W Hall, Yasuko Orba, Hirofumi Sawa
EBioMedicine, 99, 104950, 104950, 29 Dec. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Pulmonary infection with SARS-CoV-2 stimulates host immune responses and can also result in the progression of dysregulated and critical inflammation. Throughout the pandemic, the management and treatment of COVID-19 has been continuously updated with a range of antiviral drugs and immunomodulators. Monotherapy with oral antivirals has proven to be effective in the treatment of COVID-19. However, treatment should be initiated in the early stages of infection to ensure beneficial therapeutic outcomes, and there is still room for further consideration on therapeutic strategies using antivirals. METHODS: We studied the therapeutic effects of monotherapy with the oral antiviral ensitrelvir or the anti-inflammatory corticosteroid methylprednisolone and combination therapy with ensitrelvir and methylprednisolone in a delayed dosing model of hamsters infected with SARS-CoV-2. FINDINGS: Combination therapy with ensitrelvir and methylprednisolone improved respiratory conditions and reduced the development of pneumonia in hamsters even when the treatment was started after 2 days post-infection. The combination therapy led to a differential histological and transcriptomic pattern in comparison to either of the monotherapies, with reduced lung damage and down-regulation of expression of genes involved in the inflammatory response. Furthermore, we found that the combination treatment is effective in case of infection with either the highly pathogenic delta or circulating omicron variants. INTERPRETATION: Our results demonstrate the advantage of combination therapy with antiviral and corticosteroid drugs in COVID-19 treatment from the perspective of lung pathology and host inflammatory responses. FUNDING: Funding bodies are described in the Acknowledgments section.

Viral uptake and pathophysiology of the lung endothelial cells in age‐associated severe SARS‐CoV‐2 infection models
Takuya Tsumita, Ryo Takeda, Nako Maishi, Yasuhiro Hida, Michihito Sasaki, Yasuko Orba, Akihiko Sato, Shinsuke Toba, Wataru Ito, Takahito Teshirogi, Yuya Sakurai, Tomohiro Iba, Hisamichi Naito, Hitoshi Ando, Haruhisa Watanabe, Amane Mizuno, Toshiki Nakanishi, Aya Matsuda, Ren Zixiao, Ji‐Won Lee, Tadahiro Iimura, Hirofumi Sawa, Kyoko Hida
Aging Cell, 23, 2, e14050, Wiley, 14 Dec. 2023, [Corresponding author]
Scientific journal, Abstract

Thrombosis is the major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, and the pathology of vascular endothelial cells (ECs) has received much attention. Although there is evidence of the infection of ECs in human autopsy tissues, their detailed pathophysiology remains unclear due to the lack of animal model to study it. We used a mouse‐adapted SARS‐CoV‐2 virus strain in young and mid‐aged mice. Only mid‐aged mice developed fatal pneumonia with thrombosis. Pulmonary ECs were isolated from these infected mice and RNA‐Seq was performed. The pulmonary EC transcriptome revealed that significantly higher levels of viral genes were detected in ECs from mid‐aged mice with upregulation of viral response genes such as DDX58 and IRF7. In addition, the thrombogenesis‐related genes encoding PLAT, PF4, F3 PAI‐1, and P‐selectin were upregulated. In addition, the inflammation‐related molecules such as CXCL2 and CXCL10 were upregulated in the mid‐aged ECs upon viral infection. Our mouse model demonstrated that SARS‐CoV‐2 virus entry into aged vascular ECs upregulated thrombogenesis and inflammation‐related genes and led to fatal pneumonia with thrombosis. Current results of EC transcriptome showed that EC uptake virus and become thrombogenic by activating neutrophils and platelets in the aged mice, suggesting age‐associated EC response as a novel finding in human severe COVID‐19.

Ubiquitin accumulation induced by the finger and palm sub-domains of NS5 modulates the replication of West Nile virus.
Shintaro Kobayashi, Ryoko Kawakami, Chisaki Takeda, Keisuke Maezono, Passawat Thammahakin, Haruto Eguchi, Bernard M Hang'ombe, Yasuko Orba, Hirofumi Sawa, Kentaro Yoshii, Hiroaki Kariwa
Virology, 588, 109902, 109902, Nov. 2023, [International Magazine]
English, Scientific journal, West Nile virus (WNV) causes encephalitis in human and animals. WNV is phylogenetically classified into at least five distinct genetic lineages with different pathogenicity. The pathogenesis of West Nile encephalitis is affected by ubiquitin accumulation in infected cells, but the mechanism is unknown. In this study, the association between ubiquitin accumulation and WNV pathogenicity was investigated. Ubiquitin accumulation was detected in cells infected with NY99 strain belonging to lineage-1, but not FCG and Zmq16 strains belonging to lineage-2. Substitution of the Finger and Palm sub-domains of NS5 from lineage-1 to -2 decreased ubiquitin accumulation and viral replication. Furthermore, the survival rate was increased, and viral replication and ubiquitin accumulation in the brain were attenuated, in mice inoculated with the substituted WNV compared with lineage-1 WNV. Therefore, the intracellular ubiquitin accumulation induced by the Finger and Palm sub-domains of NS5 is linked to the differences in pathogenicity among WNV lineages.

Determination of the factors responsible for the tropism of SARS-CoV-2-related bat coronaviruses to Rhinolophus bat ACE2
Shigeru Fujita, Yusuke Kosugi, Izumi Kimura, Kenzo Tokunaga, Jumpei Ito, Kei Sato, Keita Matsuno, Naganori Nao, Hirofumi Sawa, Shinya Tanaka, Masumi Tsuda, Lei Wang, Yoshikata Oda, Zannatul Ferdous, Kenji Shishido, Takasuke Fukuhara, Tomokazu Tamura, Rigel Suzuki, Saori Suzuki, Hayato Ito, Yu Kaku, Naoko Misawa, Arnon Plianchaisuk, Ziyi Guo, Alfredo A. Hinay, Keiya Uriu, Jarel Elgin M. Tolentino, Luo Chen, Lin Pan, Mai Suganami, Mika Chiba, Ryo Yoshimura, Kyoko Yasuda, Keiko Iida, Naomi Ohsumi, Adam P. Strange, Shiho Tanaka, Kazuhisa Yoshimura, Kenji Sadamasu, Mami Nagashima, Hiroyuki Asakura, Isao Yoshida, So Nakagawa, Akifumi Takaori-Kondo, Kayoko Nagata, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Kazuo Takayama, Rina Hashimoto, Sayaka Deguchi, Yukio Watanabe, Ayaka Sakamoto, Naoko Yasuhara, Takao Hashiguchi, Tateki Suzuki, Kanako Kimura, Jiei Sasaki, Yukari Nakajima, Hisano Yajima, Takashi Irie, Ryoko Kawabata, Kaori Tabata, Terumasa Ikeda, Hesham Nasser, Ryo Shimizu, M. S. T. Monira Begum, Michael Jonathan, Yuka Mugita, Otowa Takahashi, Kimiko Ichihara, Chihiro Motozono, Takamasa Ueno, Mako Toyoda, Akatsuki Saito, Maya Shofa, Yuki Shibatani, Tomoko Nishiuchi, Kotaro Shirakawa
Journal of Virology, 97, 10, American Society for Microbiology, 31 Oct. 2023
Scientific journal, ABSTRACT

Differences in host angiotensin converting enzyme 2 (ACE2) genes may affect the host range of SARS-CoV-2-related coronaviruses (SC2r-CoVs) and further determine the tropism of host ACE2 for the infection receptor. However, the factor(s) responsible for determining the host tropism of SC2r-CoVs, which may in part be determined by the tropism of host ACE2 usage, remains unclear. Here, we use the pseudoviruses with the spike proteins of two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and the cells expressing ACE2 proteins of eight different Rhinolophus bat species to show that these two spikes have different tropisms for Rhinolophus bat ACE2. Through structural analysis and cell culture experiments, we demonstrate that this tropism is determined by residue 493 of the spike and residues 31 and 35 of ACE2. Our results suggest that SC2r-CoVs exhibit differential ACE2 tropism, which may be driven by adaptation to different Rhinolophus bat ACE2 proteins.

IMPORTANCE

The efficiency of infection receptor use is the first step in determining the species tropism of viruses. After the coronavirus disease 2019 pandemic, a number of SARS-CoV-2-related coronaviruses (SC2r-CoVs) were identified in Rhinolophus bats, and some of them can use human angiotensin converting enzyme 2 (ACE2) for the infection receptor without acquiring additional mutations. This means that the potential of certain SC2r-CoVs to cause spillover from bats to humans is "off-the-shelf." However, both SC2r-CoVs and Rhinolophus bat species are highly diversified, and the host tropism of SC2r-CoVs remains unclear. Here, we focus on two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and determine how the tropism of SC2r-CoVs to Rhinolophus bat ACE2 is determined at the amino acid resolution level.

Expanding diversity of bunyaviruses identified in mosquitoes.
Yasuko Orba, Yusuf Eshimutu Abu, Herman M Chambaro, Tapiwa Lundu, Walter Muleya, Yuki Eshita, Yongjin Qiu, Hayato Harima, Masahiro Kajihara, Akina Mori-Kajihara, Keita Matsuno, Michihito Sasaki, William W Hall, Bernard M Hang'ombe, Hirofumi Sawa
Scientific reports, 13, 1, 18165, 18165, 24 Oct. 2023, [International Magazine]
English, Scientific journal, Mosquitoes interact with various organisms in the environment, and female mosquitoes in particular serve as vectors that directly transmit a number of microorganisms to humans and animals by blood-sucking. Comprehensive analysis of mosquito-borne viruses has led to the understanding of the existence of diverse viral species and to the identification of zoonotic arboviruses responsible for significant outbreaks and epidemics. In the present study on mosquito-borne bunyaviruses we employed a broad-spectrum RT-PCR approach and identified eighteen different additional species in the Phenuiviridae family and also a number of related but unclassified bunyaviruses in mosquitoes collected in Zambia. The entire RNA genome segments of the newly identified viruses were further analyzed by RNA sequencing with a ribonuclease R (RNase R) treatment to reduce host-derived RNAs and enrich viral RNAs, taking advantage of the dsRNA panhandle structure of the bunyavirus genome. All three or four genome segments were identified in eight bunyavirus species. Furthermore, L segments of three different novel viruses related to the Leishbunyaviridae were found in mosquitoes together with genes from the suspected host, the Crithidia parasite. In summary, our virus detection approach using a combination of broad-spectrum RT-PCR and RNA sequencing analysis with a simple virus enrichment method allowed the discovery of novel bunyaviruses. The diversity of bunyaviruses is still expanding and studies on this will allow a better understanding of the ecology of hematophagous mosquitoes.

2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses.
Kentaro Uemura, Haruaki Nobori, Akihiko Sato, Shinsuke Toba, Shinji Kusakabe, Michihito Sasaki, Koshiro Tabata, Keita Matsuno, Naoyoshi Maeda, Shiori Ito, Mayu Tanaka, Yuki Anraku, Shunsuke Kita, Mayumi Ishii, Kayoko Kanamitsu, Yasuko Orba, Yoshiharu Matsuura, William W Hall, Hirofumi Sawa, Hiroshi Kida, Akira Matsuda, Katsumi Maenaka
Proceedings of the National Academy of Sciences of the United States of America, 120, 42, e2304139120, 17 Oct. 2023, [International Magazine]
English, Scientific journal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral ribonucleoside analogue that exhibited antiviral activity against several positive-sense single-stranded RNA (ssRNA+) viruses, such as DENV, SARS-CoV-2, and its variants of concern, including the currently circulating Omicron subvariants. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with DENV2 or SARS-CoV-2 in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against DENV and SARS-CoV-2 but other ssRNA+ viruses.

Development of flavivirus subviral particles with low cross-reactivity by mutations of a distinct antigenic domain.
Koshiro Tabata, Yukari Itakura, Takuma Ariizumi, Manabu Igarashi, Hiroko Kobayashi, Kittiya Intaruck, Mai Kishimoto, Shintaro Kobayashi, William W Hall, Michihito Sasaki, Hirofumi Sawa, Yasuko Orba
Applied microbiology and biotechnology, 13 Oct. 2023, [International Magazine]
English, Scientific journal, The most conserved fusion loop (FL) domain present in the flavivirus envelope protein has been reported as a dominant epitope for cross-reactive antibodies to mosquito-borne flaviviruses (MBFVs). As a result, establishing accurate serodiagnosis for MBFV infections has been difficult as anti-FL antibodies are induced by both natural infection and following vaccination. In this study, we modified the most conserved FL domain to overcome this cross-reactivity. We showed that the FL domain of lineage I insect-specific flavivirus (ISFV) has differences in antigenicity from those of MBFVs and lineage II ISFV and determined the key amino acid residues (G106, L107, or F108), which contribute to the antigenic difference. These mutations were subsequently introduced into subviral particles (SVPs) of dengue virus type 2 (DENV2), Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV). In indirect enzyme-linked immunosorbent assays (ELISAs), these SVP mutants when used as antigens reduced the binding of cross-reactive IgG and total Ig induced by infection of ZIKV, JEV, and WNV in mice and enabled the sensitive detection of virus-specific antibodies. Furthermore, immunization of ZIKV or JEV SVP mutants provoked the production of antibodies with lower cross-reactivity to heterologous MBFV antigens compared to immunization with the wild-type SVPs in mice. This study highlights the effectiveness of introducing mutations in the FL domain in MBFV SVPs with lineage I ISFV-derived amino acids to produce SVP antigens with low cross-reactivity and demonstrates an improvement in the accuracy of indirect ELISA-based serodiagnosis for MBFV infections. KEY POINTS: • The FL domain of Lineage I ISFV has a different antigenicity from that of MBFVs. • Mutated SVPs reduce the binding of cross-reactive antibodies in indirect ELISAs. • Inoculation of mutated SVPs induces antibodies with low cross-reactivity.

Prevalence and Genomic Characterization of Rotavirus A from Domestic Pigs in Zambia: Evidence for Possible Porcine–Human Interspecies Transmission
Joseph Ndebe, Hayato Harima, Herman Moses Chambaro, Michihito Sasaki, Junya Yamagishi, Annie Kalonda, Misheck Shawa, Yongjin Qiu, Masahiro Kajihara, Ayato Takada, Hirofumi Sawa, Ngonda Saasa, Edgar Simulundu
Pathogens, 12, 10, 1199, 1199, MDPI AG, 27 Sep. 2023, [Peer-reviewed]
English, Scientific journal, Rotavirus is a major cause of diarrhea globally in animals and young children under 5 years old. Here, molecular detection and genetic characterization of porcine rotavirus in smallholder and commercial pig farms in the Lusaka Province of Zambia were conducted. Screening of 148 stool samples by RT-PCR targeting the VP6 gene revealed a prevalence of 22.9% (34/148). Further testing of VP6-positive samples with VP7-specific primers produced 12 positives, which were then Sanger-sequenced. BLASTn of the VP7 positives showed sequence similarity to porcine and human rotavirus strains with identities ranging from 87.5% to 97.1%. By next-generation sequencing, the full-length genetic constellation of the representative strains RVA/pig-wt/ZMB/LSK0137 and RVA/pig-wt/ZMB/LSK0147 were determined. Genotyping of these strains revealed a known Wa-like genetic backbone, and their genetic constellations were G4-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[13]-I5-R1-C1-M1-A8-N1-T1-E1-H1, respectively. Phylogenetic analysis revealed that these two viruses might have their ancestral origin from pigs, though some of their gene segments were related to human strains. The study shows evidence of reassortment and possible interspecies transmission between pigs and humans in Zambia. Therefore, the “One Health” surveillance approach for rotavirus A in animals and humans is recommended to inform the design of effective control measures.

ザンビアにおけるブタインフルエンザの疫学調査　　　　　　　　　　　　　　　
播磨 勇人, 奥谷 公亮, 梶原 将大, 小川 寛人, Simulundu Edgar, Bwalya Eugene, 邱 永晋, 迫田 義博, 西藤 岳彦, Hang' ombe Bernard, 澤 洋文, Mweene Aaron, 高田 礼人
日本獣医学会学術集会講演要旨集, 166回, 154, 154, (公社)日本獣医学会, Sep. 2023
Japanese

Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5
Tomokazu Tamura, Daichi Yamasoba, Yoshitaka Oda, Jumpei Ito, Tomoko Kamasaki, Naganori Nao, Rina Hashimoto, Yoichiro Fujioka, Rigel Suzuki, Lei Wang, Hayato Ito, Yukie Kashima, Izumi Kimura, Mai Kishimoto, Masumi Tsuda, Hirofumi Sawa, Kumiko Yoshimatsu, Yuki Yamamoto, Tetsuharu Nagamoto, Jun Kanamune, Yutaka Suzuki, Yusuke Ohba, Saori Suzuki, Marie Kato, Zannatul Ferdous, Hiromi Mouri, Kenji Shishido, Naoko Misawa, Keiya Uriu, Yusuke Kosugi, Shigeru Fujita, Mai Suganami, Mika Chiba, Ryo Yoshimura, So Nakagawa, Jiaqi Wu, Akifumi Takaori-Kondo, Kotaro Shirakawa, Kayoko Nagata, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Takao Hashiguchi, Tateki Suzuki, Kanako Kimura, Jiei Sasaki, Yukari Nakajima, Ayaka Sakamoto, Naoko Yasuhara, Takashi Irie, Ryoko Kawabata, Terumasa Ikeda, Hesham Nasser, Ryo Shimizu, Monira Begum, Otowa Takahashi, Kimiko Ichihara, Takamasa Ueno, Chihiro Motozono, Mako Toyoda, Akatsuki Saito, Yuri L. Tanaka, Erika P. Butlertanaka, Maya Shofa, Kaori Tabata, Isao Yokota, Keita Matsuno, Kazuo Takayama, Shinya Tanaka, Kei Sato, Takasuke Fukuhara
Communications Biology, 6, 1, Springer Science and Business Media LLC, 24 Jul. 2023
Scientific journal, Abstract

The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants.

Generation and characterization of a genetically modified live rabies vaccine strain with attenuating mutations in multiple viral proteins and evaluation of its potency in dogs.
Fumiki Izumi, Shoya Miyamoto, Tatsunori Masatani, Michihito Sasaki, Kazuo Kawakami, Tatsuki Takahashi, Takuro Fujiwara, Yuji Fujii, Misuzu Okajima, Shoko Nishiyama, Hirofumi Sawa, Makoto Sugiyama, Naoto Ito
Vaccine, 41, 33, 4907, 4917, 01 Jul. 2023, [International Magazine]
English, Scientific journal, Live rabies vaccines have advantageous features that can facilitate mass vaccination for dogs, the most important reservoirs/transmitters of rabies. However, some live vaccine strains have problems in their safety, namely, risks from the residual pathogenicity and the pathogenic reversion of live vaccine strains. The reverse genetics system of rabies virus provides a feasible option to improve the safety of a live vaccine strain by, for example, artificially introducing attenuating mutations into multiple viral proteins. It was previously demonstrated in separate studies that introduction of amino acid residues Leu at position 333 in the viral glycoprotein (G333), Ser at G194, and Leu/His at positions 273/394 in the nucleoprotein (N273/394) enhance the safety of a live vaccine strain. In this study, to test our hypothesis that combinational introduction of these residues would significantly increase the safety level of a vaccine strain, we generated a novel live vaccine candidate, ERA-NG2, that is attenuated by mutations at N273/394 and G194/333, and we examined its safety and immunogenicity in mice and dogs. ERA-NG2 did not cause any clinical signs in mice after intracerebral inoculation. After 10 passages in suckling mouse brains, ERA-NG2 retained all of the introduced mutations except the mutation at N394 and the highly attenuated phenotype. These findings indicate that the ERA-NG2 is highly and stably attenuated. After confirming that ERA-NG2 induced a virus-neutralizing antibody (VNA) response and protective immunity in mice, we immunized dogs intramuscularly with a single dose (105-7 focus-forming units) of ERA-NG2 and found that, at all of the tested doses, the strain induced a VNA response in dogs without inducing any clinical signs. These findings demonstrate that ERA-NG2 has a high level of safety and a substantial level of immunogenicity in dogs and thus is a promising live vaccine candidate that can facilitate vaccination in dogs.

Impact of imprinted immunity induced by mRNA vaccination in an experimental animal model.
Shigeru Fujita, Keiya Uriu, Lin Pan, Naganori Nao, Koshiro Tabata, Mai Kishimoto, Yukari Itakura, Hirofumi Sawa, Izumi Kida, Tomokazu Tamura, Takasuke Fukuhara, Jumpei Ito, Keita Matsuno, Kei Sato
The Journal of infectious diseases, 27 Jun. 2023, [International Magazine]
English, Scientific journal, The emergence of SARS-CoV-2 Omicron variants has led to concerns that ancestral SARS-CoV-2-based vaccines may not be effective against newly emerging Omicron subvariants. The concept of "imprinted immunity" suggests that individuals vaccinated with ancestral virus-based vaccines may not develop effective immunity against newly emerging Omicron subvariants, such as BQ.1.1 and XBB.1. Here, we investigated this possibility using hamsters. While natural infection induced effective antiviral immunity, breakthrough infections in hamsters with BQ.1.1 and XBB.1 Omicron subvariants after receiving the 3-dose mRNA-LNP vaccine resulted in only faintly induced humoral immunity, supporting the possibility of imprinted immunity.

Surveillance, Isolation, and Genetic Characterization of Bat Herpesviruses in Zambia.
Hayato Harima, Yongjin Qiu, Junya Yamagishi, Masahiro Kajihara, Katendi Changula, Kosuke Okuya, Mao Isono, Tomoyuki Yamaguchi, Hirohito Ogawa, Naganori Nao, Michihito Sasaki, Edgar Simulundu, Aaron S Mweene, Hirofumi Sawa, Kanako Ishihara, Bernard M Hang'ombe, Ayato Takada
Viruses, 15, 6, 13 Jun. 2023, [International Magazine]
English, Scientific journal, Bats are of significant interest as reservoirs for various zoonotic viruses with high diversity. During the past two decades, many herpesviruses have been identified in various bats worldwide by genetic approaches, whereas there have been few reports on the isolation of infectious herpesviruses. Herein, we report the prevalence of herpesvirus infection of bats captured in Zambia and genetic characterization of novel gammaherpesviruses isolated from striped leaf-nosed bats (Macronycteris vittatus). By our PCR screening, herpesvirus DNA polymerase (DPOL) genes were detected in 29.2% (7/24) of Egyptian fruit bats (Rousettus aegyptiacus), 78.1% (82/105) of Macronycteris vittatus, and one Sundevall's roundleaf bat (Hipposideros caffer) in Zambia. Phylogenetic analyses of the detected partial DPOL genes revealed that the Zambian bat herpesviruses were divided into seven betaherpesvirus groups and five gammaherpesvirus groups. Two infectious strains of a novel gammaherpesvirus, tentatively named Macronycteris gammaherpesvirus 1 (MaGHV1), were successfully isolated from Macronycteris vittatus bats, and their complete genomes were sequenced. The genome of MaGHV1 encoded 79 open reading frames, and phylogenic analyses of the DNA polymerase and glycoprotein B demonstrated that MaGHV1 formed an independent lineage sharing a common origin with other bat-derived gammaherpesviruses. Our findings provide new information regarding the genetic diversity of herpesviruses maintained in African bats.

Genome Sequence of a Clinical Isolate of the Human Pathogenic Strain "Candidatus Borrelia fainii" Qtaro.
Kentaro Itokawa, Kozue Sato, Yongjin Qiu, Jyunya Yamagishi, Katendi Changula, Naoko Kawai, Kyoko Hayashida, Joseph Ndebe, Bernard Mudenda Hang'ombe, Hirofumi Sawa, Shinji Kasai, Yukihiro Akeda, Hiroki Kawabata
Microbiology resource announcements, 12, 5, e0131822, 19 Apr. 2023, [International Magazine]
English, Scientific journal, We report sequences of the complete linear chromosome and five linear plasmids of the relapsing fever spirochete "Candidatus Borrelia fainii" Qtaro. The chromosome sequence of 951,861 bp and the 243,291 bp of plasmid sequences were predicted to contain 852 and 239 protein-coding genes, respectively. The predicted total GC content was 28.4%.

Morphogenesis of Bullet-Shaped Rabies Virus Particles Regulated by TSG101.
Yukari Itakura, Koshiro Tabata, Takeshi Saito, Kittiya Intaruck, Nijiho Kawaguchi, Mai Kishimoto, Shiho Torii, Shintaro Kobayashi, Naoto Ito, Michiko Harada, Satoshi Inoue, Ken Maeda, Ayato Takada, William W Hall, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
Journal of virology, 97, 5, e0043823, 12 Apr. 2023, [International Magazine]
English, Scientific journal, Viral protein assembly and virion budding are tightly regulated to enable the proper formation of progeny virions. At this late stage in the virus life cycle, some enveloped viruses take advantage of the host endosomal sorting complex required for transport (ESCRT) machinery, which contributes to the physiological functions of membrane modulation and abscission. Bullet-shaped viral particles are unique morphological characteristics of rhabdoviruses; however, the involvement of host factors in rhabdovirus infection and, specifically, the molecular mechanisms underlying virion formation are not fully understood. In the present study, we used a small interfering RNA (siRNA) screening approach and found that the ESCRT-I component TSG101 contributes to the propagation of rabies virus (RABV). We demonstrated that the matrix protein (M) of RABV interacts with TSG101 via the late domain containing the PY and YL motifs, which are conserved in various viral proteins. Loss of the YL motif in the RABV M or the downregulation of host TSG101 expression resulted in the intracellular aggregation of viral proteins and abnormal virus particle formation, indicating a defect in the RABV assembly and budding processes. These results indicate that the interaction of the RABV M and TSG101 is pivotal for not only the efficient budding of progeny RABV from infected cells but also for the bullet-shaped virion morphology. IMPORTANCE Enveloped viruses bud from cells with the host lipid bilayer. Generally, the membrane modulation and abscission are mediated by host ESCRT complexes. Some enveloped viruses utilize their late (L-) domain to interact with ESCRTs, which promotes viral budding. Rhabdoviruses form characteristic bullet-shaped enveloped virions, but the underlying molecular mechanisms involved remain elusive. Here, we showed that TSG101, one of the ESCRT components, supports rabies virus (RABV) budding and proliferation. TSG101 interacted with RABV matrix protein via the L-domain, and the absence of this interaction resulted in intracellular virion accumulation and distortion of the morphology of progeny virions. Our study reveals that virion formation of RABV is highly regulated by TSG101 and the virus matrix protein.

Surveillance and Phylogenetic Characterisation of Avian Influenza Viruses Isolated from Wild Waterfowl in Zambia in 2015, 2020, and 2021
Annie Kalonda, Ngonda Saasa, Masahiro Kajihara, Naganori Nao, Ladislav Moonga, Joseph Ndebe, Akina Mori-Kajihara, Andrew Nalishuwa Mukubesa, Mulemba Samutela, Samuel Munjita, Yoshihiro Sakoda, Hirofumi Sawa, Ayato Takada, Edgar Simulundu
Transboundary and Emerging Diseases, 2023, 1, 16, Hindawi Limited, 01 Mar. 2023
Scientific journal, In recent years, the southern African region has experienced repeated incursions of highly pathogenic avian influenza viruses (HPAIVs), with wild migratory birds being implicated in the spread. To understand the profile of avian influenza viruses (AIVs) circulating in Zambia, we surveyed wild waterfowl for AIVs and phylogenetically characterised the isolates detected in 2015, 2020, and 2021. A total of 2,851 faecal samples of wild waterfowl were collected from Lochinvar National Park in the Southern Province of Zambia. During the study period, 85 (3.0%) low pathogenicity AIVs belonging to various subtypes were isolated, with H2N9, H8N4, and H10N8 being reported for the first time in avian species in Africa. The majority of the isolates were detected from glossy ibis (order Pelecaniformes) making it the first report of AIV from these birds in Zambia. Phylogenetic analysis of all eight gene segments of the 30 full genomes obtained in this study revealed that all the isolates belonged to the Eurasian lineage with their closest relatives being viruses isolated from wild and/or domestic birds in Bangladesh, Belgium, Egypt, Georgia, Mongolia, the Netherlands, and South Africa. Additionally, the Zambian viruses were grouped into distinct clusters based on the year of isolation. While no notifiable AIVs of the H5 or H7 subtypes were detected in wild birds in Zambia, viral internal protein genes of some viruses were closely related to H7 low pathogenicity AIVs. This study shows that periodically, a considerable diversity of AIV subtypes are introduced into the Zambian ecosystem by wild migratory waterfowl. The findings highlight the importance of continuous surveillance and monitoring of AIVs in wild waterfowl, including birds traditionally not considered to be major AIV reservoirs, for a better understanding of the eco-epidemiology and evolutionary dynamics of AIVs in Africa.

Structure-activity relationship studies of anti-bunyaviral cap-dependent endonuclease inhibitors.
Yoshiyuki Taoda, Akihiko Sato, Shinsuke Toba, Yuto Unoh, Makoto Kawai, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa
Bioorganic & medicinal chemistry letters, 83, 129175, 129175, 01 Mar. 2023, [International Magazine]
English, Scientific journal, Bunyaviruses, including the Lassa virus (LASV), are known to cause hemorrhagic fever and have a high fatality rate among hospitalized patients, as there are few effective treatments. We focused on the fact that bunyaviruses use cap-dependent endonuclease (CEN) for viral replication, which is similar to influenza viruses. This led us to screen carbamoyl pyridone bicycle (CAB) compounds, which compose a series of baloxavir acid (BXA) derivatives, against lymphocytic choriomeningitis virus (LCMV) and Junin virus (JUNV) among the bunyaviruses. This led to the discovery of 1c, which has potent anti-bunyaviral activities. In SAR studies, we found that a large lipophilic side chain is preferred for the 1-position of the CAB scaffold, similar to the influenza CEN inhibitor, and that a small alkyl group for the 3-position shows high activity. Moreover, the 7‑carboxyl group of the scaffold is essential for anti-bunyaviral activities, and the antiviral activity is reduced by conversion to various carboxylic acid bioisosteres. The SAR results are discussed using a binding model of 9d in the active center of the known LCMV CEN crystal structure. These compounds show promise as broad-spectrum anti-bunyavirus therapeutics, given their relatively favorable metabolic stability and PK profiles.

Detection of Old and New World Relapsing Fever Borreliae in Ornithodoros Ticks Collected from Warthog Burrows in Zambia.
Yongjin Qiu, Herman M Chambaro, Kozue Sato, David Squarre, Edgar Simulundu, Masahiro Kajihara, Katendi Changula, Manyando Simbotwe, Hayato Harima, Joseph Ndebe, Ladslav Moonga, Ryo Nakao, Ayato Takada, Bernard Mudenda Hang'ombe, Hirofumi Sawa, Hiroki Kawabata
Microorganisms, 11, 1, 12 Jan. 2023, [International Magazine]
English, Scientific journal, Relapsing fever (RF) is an arthropod-borne disease caused by Borrelia spirochete, which is one of the major public health concerns in endemic regions including Africa. However, information on Borrelia&nbsp;spirochetes is limited in Zambia. Here, we investigate the Borrelia&nbsp;spirochetes harbored by Ornithodoros ticks in Zambian National Parks. We analyzed 182 DNA samples pooled from 886 Ornithodoros ticks. Of these, 43 tested positive, and their sequence revealed that the ticks harbored both Old and New World RF borreliae. This research presents the first evidence of Old-World RF borreliae in Zambia. The New World RF borreliae detected herein differed from the Candidatus Borrelia fainii previously reported in Zambia and were closely related to the pathogenic Borrelia sp. VS4 identified in Tanzania. Additionally, Borrelia theileri was recently reported in Zambia. Hence, at least four different Borrelia species occur in Zambia, and the organisms causing relapsing fever there might be more complex than previously thought. We empirically confirmed that real-time PCR with TaqMan minor groove binder probes accurately and simultaneously detected both Old and New World RF. In this manner, they could facilitate quantitative analyses of both types of RF borreliae. Subsequent investigations should endeavor to isolate the aforementioned Borrelia spp. and perform serosurveys on patients with RF.

Current status and molecular epidemiology of rabies virus from different hosts and regions in Malawi.
Henson Kainga, Elisha Chatanga, Marvin Collen Phonera, John Pilate Kothowa, Precious Dzimbiri, Gladson Kamwendo, Malala Mulavu, Cynthia Sipho Khumalo, Katendi Changula, Herman Chambaro, Hayato Harima, Masahiro Kajihara, Kholiwe Mkandawire, Patrick Chikungwa, Julius Chulu, Gilson Njunga, Simbarashe Chitanga, Benjamin Mubemba, Michihito Sasaki, Yasuko Orba, Yongjin Qiu, Junya Yamagishi, Edgar Simulundu, Ayato Takada, Boniface Namangala, Hirofumi Sawa, Walter Muleya
Archives of virology, 168, 2, 61, 61, 12 Jan. 2023, [International Magazine]
English, Scientific journal, Although rabies is endemic in Malawi, there have been no studies in which rabies virus was systematically investigated and characterized in multiple animal hosts in that country. In order to provide molecular epidemiological data on rabies virus in Malawi, 683 suspected rabies case reports from 2008 to 2021 were examined, and 46 (dog = 40, cow = 5, and cat = 1) viable rabies-positive brain samples archived at the Central Veterinary Laboratory (CVL), Lilongwe, Malawi, were analyzed genetically. The results showed an increase in the submission of brain samples from 2008 to 2010, with the highest number of submissions observed in 2020. Of the 683 case reports analyzed for the period under review, 38.1% (260/683) (CI: 34.44 - 41.84) were confirmed by direct fluorescent antibody test. Among the confirmed cases, 65.4% (170/260) (CI: 59.23 - 71.09) were canine rabies. Further, phylogenetic analysis revealed that sequences from different animal hosts clustered together within the Africa 1b lineage, suggesting that the strains circulating in livestock are similar to those in domestic dogs. This finding supports the hypothesis that canine rabies is spilling over to livestock and emphasizes the need for further studies to provide data for effective control of rabies in Malawi.

Isolation and Characterization of Distinct Rotavirus A in Bat and Rodent Hosts.
Mai Kishimoto, Masahiro Kajihara, Koshiro Tabata, Yukari Itakura, Shinsuke Toba, Seiya Ozono, Yuko Sato, Tadaki Suzuki, Naoto Ito, Katendi Changula, Yongjin Qiu, Akina Mori-Kajihara, Yoshiki Eto, Hayato Harima, Daniel Mwizabi, Bernard M Hang'ombe, William W Hall, Ayato Takada, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
Journal of virology, 97, 1, e0145522, 12 Jan. 2023, [International Magazine]
English, Scientific journal, Rotavirus A (RVA) causes diarrheal disease in humans and various animals. Recent studies have identified bat and rodent RVAs with evidence of zoonotic transmission and genome reassortment. However, the virological properties of bat and rodent RVAs with currently identified genotypes still need to be better clarified. Here, we performed virus isolation-based screening for RVA in animal specimens and isolated RVAs (representative strains: 16-06 and MpR12) from Egyptian fruit bat and Natal multimammate mouse collected in Zambia. Whole-genome sequencing and phylogenetic analysis revealed that the genotypes of bat RVA 16-06 were identical to that of RVA BATp39 strain from the Kenyan fruit bat, which has not yet been characterized. Moreover, all segments of rodent RVA MpR12 were highly divergent and assigned to novel genotypes, but RVA MpR12 was phylogenetically closer to bat RVAs than to other rodent RVAs, indicating a unique evolutionary history. We further investigated the virological properties of the isolated RVAs. In brief, we found that 16-06 entered cells by binding to sialic acids on the cell surface, while MpR12 entered in a sialic acid-independent manner. Experimental inoculation of suckling mice with 16-06 and MpR12 revealed that these RVAs are causative agents of diarrhea. Moreover, 16-06 and MpR12 demonstrated an ability to infect and replicate in a 3D-reconstructed primary human intestinal epithelium with comparable efficiency to the human RVA. Taken together, our results detail the unique genetic and virological features of bat and rodent RVAs and demonstrate the need for further investigation of their zoonotic potential. IMPORTANCE Recent advances in nucleotide sequence detection methods have enabled the detection of RVA genomes from various animals. These studies have discovered multiple divergent RVAs and have resulted in proposals for the genetic classification of novel genotypes. However, most of these RVAs have been identified via dsRNA viral genomes and not from infectious viruses, and their virological properties, such as cell/host tropisms, transmissibility, and pathogenicity, are unclear and remain to be clarified. Here, we successfully isolated RVAs with novel genome constellations from three bats and one rodent in Zambia. In addition to whole-genome sequencing, the isolated RVAs were characterized by glycan-binding affinity, pathogenicity in mice, and infectivity to the human gut using a 3D culture of primary intestinal epithelium. Our study reveals the first virological properties of bat and rodent RVAs with high genetic diversity and unique evolutional history and provides basic knowledge to begin estimating the potential of zoonotic transmission.

Field-deployable multiplex detection method of SARS-CoV-2 and influenza virus using loop-mediated isothermal amplification and DNA chromatography.
Kyoko Hayashida, Alejandro Garcia, Lavel Chinyama Moonga, Tatsuki Sugi, Kodera Takuya, Mitsuo Kawase, Fumihiro Kodama, Atsushi Nagasaka, Nobuhisa Ishiguro, Ayato Takada, Masahiro Kajihara, Naganori Nao, Masashi Shingai, Hiroshi Kida, Yasuhiko Suzuki, William W Hall, Hirofumi Sawa, Junya Yamagishi
PloS one, 18, 5, e0285861, 2023, [International Magazine]
English, Scientific journal, A novel multiplex loop-mediated isothermal amplification (LAMP) method combined with DNA chromatography was developed for the simultaneous detection of three important respiratory disease-causing viruses: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus. Amplification was performed at a constant temperature, and a positive result was confirmed by a visible colored band. An in-house drying protocol with trehalose was used to prepare the dried format multiplex LAMP test. Using this dried multiplex LAMP test, the analytical sensitivity was determined to be 100 copies for each viral target and 100-1000 copies for the simultaneous detection of mixed targets. The multiplex LAMP system was validated using clinical COVID-19 specimens and compared with the real-time qRT-PCR method as a reference test. The determined sensitivity of the multiplex LAMP system for SARS-CoV-2 was 71% (95% CI: 0.62-0.79) for cycle threshold (Ct) ≤ 35 samples and 61% (95% CI: 0.53-0.69) for Ct ≤40 samples. The specificity was 99% (95%CI: 0.92-1.00) for Ct ≤35 samples and 100% (95%CI: 0.92-1.00) for the Ct ≤40 samples. The developed simple, rapid, low-cost, and laboratory-free multiplex LAMP system for the two major important respiratory viral diseases, COVID-19 and influenza, is a promising field-deployable diagnosis tool for the possible future 'twindemic, ' especially in resource-limited settings.

Monitoring fusion kinetics of viral and target cell membranes in living cells using a SARS-CoV-2 spike-protein-mediated membrane fusion assay
Hesham Nasser, Ryo Shimizu, Jumpei Ito, Akatsuki Saito, Kei Sato, Terumasa Ikeda, Keita Matsuno, Naganori Nao, Hirofumi Sawa, Mai Kishimoto, Shinya Tanaka, Masumi Tsuda, Lei Wang, Yoshikata Oda, Marie Kato, Zannatul Ferdous, Hiromi Mouri, Kenji Shishido, Takasuke Fukuhara, Tomokazu Tamura, Rigel Suzuki, Hayato Ito, Daichi Yamasoba, Izumi Kimura, Naoko Misawa, Keiya Uriu, Yusuke Kosugi, Shigeru Fujita, Mai Suganami, Mika Chiba, Ryo Yoshimura, So Nakagawa, Jiaqi Wu, Akifumi Takaori-Kondo, Kotaro Shirakawa, Kayoko Nagata, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Takashi Irie, Ryoko Kawabata, MST Monira Begum, Otowa Takahashi, Kimiko Ichihara, Takamasa Ueno, Chihiro Motozono, Mako Toyoda, Yuri L. Tanaka, Erika P. Butlertanaka, Maya Shofa, Kazuo Takayama, Rina Hashimoto, Sayaka Deguchi, Takao Hashiguchi, Tateki Suzuki, Kanako Kimura, Jiei Sasaki, Yukari Nakajima, Kaori Tabata
STAR Protocols, 3, 4, 101773, 101773, Elsevier BV, Dec. 2022
Scientific journal

Luna Virus and Helminths in Wild Mastomys natalensis in Two Contrasting Habitats in Zambia: Risk Factors and Evidence of Virus Dissemination in Semen.
Samuel Munalula Munjita, Given Moonga, Andrew Nalishuwa Mukubesa, Joseph Ndebe, Benjamin Mubemba, Manu Vanaerschot, Cristina Tato, John Tembo, Nathan Kapata, Simbarashe Chitanga, Katendi Changula, Mashiro Kajihara, Walter Muleya, Ayato Takada, Elisabeth Fichet-Calvet, Alimuddin Zumla, Hirofumi Sawa, Matthew Bates, Sody Munsaka, Edgar Simulundu
Pathogens (Basel, Switzerland), 11, 11, 14 Nov. 2022, [International Magazine]
English, Scientific journal, Transmission dynamics and the maintenance of mammarenaviruses in nature are poorly understood. Using metagenomic next-generation sequencing (mNGS) and RT-PCR, we investigated the presence of mammarenaviruses and co-infecting helminths in various tissues of 182 Mastomys natalensis rodents and 68 other small mammals in riverine and non-riverine habitats in Zambia. The Luna virus (LUAV) genome was the only mammarenavirus detected (7.7%; 14/182) from M. natalensis. Only one rodent from the non-riverine habitat was positive, while all six foetuses from one pregnant rodent carried LUAV. LUAV-specific mNGS reads were 24-fold higher in semen than in other tissues from males. Phylogenetically, the viruses were closely related to each other within the LUAV clade. Helminth infections were found in 11.5% (21/182) of M. natalensis. LUAV-helminth co-infections were observed in 50% (7/14) of virus-positive rodents. Juvenility (OR = 9.4; p = 0.018; 95% CI: 1.47-59.84), nematodes (OR = 15.5; p = 0.001; 95% CI: 3.11-76.70), cestodes (OR = 10.8; p = 0.025; 95% CI: 1.35-86.77), and being male (OR = 4.6; p = 0.036; 95% CI: 1.10-18.90) were associated with increased odds of LUAV RNA detection. The role of possible sexual and/or congenital transmission in the epidemiology of LUAV infections in rodents requires further study, along with the implications of possible helminth co-infection.

Seroprevalence and Associated Risk Factors of Rift Valley Fever in Livestock from Three Ecological Zones of Malawi.
Henson Kainga, Marvin Collen Phonera, Elisha Chatanga, Simegnew Adugna Kallu, Prudence Mpundu, Mulemba Samutela, Herman Moses Chambaro, Masahiro Kajihara, Doreen Mainza Shempela, Jay Sikalima, Walter Muleya, Misheck Shawa, Julius Chulu, Gilson Njunga, Martin Simuunza, Ayato Takada, Hirofumi Sawa, Edgar Simulundu, Ngonda Saasa
Pathogens (Basel, Switzerland), 11, 11, 14 Nov. 2022, [International Magazine]
English, Scientific journal, The epidemiology of Rift Valley fever (RVF) is poorly understood in Malawi. Here, a cross-sectional study was conducted (March-June 2020) to investigate the seroprevalence and potential risk factors of RVF virus (RVFV) in cattle, goats, and sheep in three ecological zones of Malawi. A total of 1523 serum samples were tested for anti-RVFV IgG and IgM antibodies by ELISA. Additionally, a questionnaire survey was used to assess potential RVF risk factors. The overall seroprevalence was 17.14% (261/1523; 95% CI = 15.33-19.11) for individual livestock and 33.24% (120/361; 95% CI = 28.18-38.11) for the livestock herd. Seroprevalence was significantly high in sheep (25.68%, 95% CI = 19.31-33.26) compared with cattle (21.35%, 95% CI = 18.74-24.22) and goats (7.72%, 95% CI = 5.72-10.34), (p = 0.047). At the individual livestock level, the risk was elevated in female livestock (OR: 1.74, 95% CI = 1.08-12.82) (p = 0.016), while at the herd level, areas receiving approximately 1001-1500 mm of rainfall (OR: 2.47, 95% CI = 1.14-5.37) (p = 0.022), areas of rainfall amount greater than approximately 1600 mm (OR: 2.239, 95% CI = 1.07-8.82) (p = 0.023), and mixed species herds (OR: 10.410, 95% CI = 3.04-35.59) (p = 0.001), were significant risk factors. The detection of IgM antibodies confirmed active circulation of RVFV in Malawi. Therefore, monitoring of RVF in animals, humans, and vectors using a "One Health" approach, along with community sensitization among the high-risk populations, could help mitigate the threat posed by this zoonotic disease in Malawi.

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant.
Akatsuki Saito, Tomokazu Tamura, Jiri Zahradnik, Sayaka Deguchi, Koshiro Tabata, Yuki Anraku, Izumi Kimura, Jumpei Ito, Daichi Yamasoba, Hesham Nasser, Mako Toyoda, Kayoko Nagata, Keiya Uriu, Yusuke Kosugi, Shigeru Fujita, Maya Shofa, Mst Monira Begum, Ryo Shimizu, Yoshitaka Oda, Rigel Suzuki, Hayato Ito, Naganori Nao, Lei Wang, Masumi Tsuda, Kumiko Yoshimatsu, Jin Kuramochi, Shunsuke Kita, Kaori Sasaki-Tabata, Hideo Fukuhara, Katsumi Maenaka, Yuki Yamamoto, Tetsuharu Nagamoto, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Takamasa Ueno, Gideon Schreiber, Akifumi Takaori-Kondo, Kotaro Shirakawa, Hirofumi Sawa, Takashi Irie, Takao Hashiguchi, Kazuo Takayama, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, Kei Sato
Cell host & microbe, 30, 11, 1540, 1555, 09 Nov. 2022, [International Magazine]
English, Scientific journal, The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.

S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters.
Michihito Sasaki, Koshiro Tabata, Mai Kishimoto, Yukari Itakura, Hiroko Kobayashi, Takuma Ariizumi, Kentaro Uemura, Shinsuke Toba, Shinji Kusakabe, Yuki Maruyama, Shun Iida, Noriko Nakajima, Tadaki Suzuki, Shinpei Yoshida, Haruaki Nobori, Takao Sanaki, Teruhisa Kato, Takao Shishido, William W Hall, Yasuko Orba, Akihiko Sato, Hirofumi Sawa
Science translational medicine, 15, 679, eabq4064, 03 Nov. 2022, [International Magazine]
English, Scientific journal, In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity, but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2 infection in vitro, few have proven to be effective in vivo. Here, we show that oral administration of S-217622 (ensitrelvir), an inhibitor of SARS-CoV-2 main protease (Mpro, also known as 3C-like protease), decreases viral load and ameliorates disease severity in SARS-CoV-2-infected hamsters. S-217622 inhibited viral proliferation at low nanomolar to sub-micromolar concentrations in cells. Oral administration of S-217622 demonstrated favorable pharmacokinetic properties and accelerated recovery from acute SARS-CoV-2 infection in hamster recipients. Moreover, S-217622 exerted antiviral activity against SARS-CoV-2 variants of concern (VOCs), including the highly pathogenic Delta variant and the recently emerged Omicron BA.5 and BA.2.75 variants. Overall, our study provides evidence that S-217622, an antiviral agent that is under evaluation in a phase 3 clinical trial (clinical trial registration no. jRCT2031210350), possesses remarkable antiviral potency and efficacy against SARS-CoV-2 and is a prospective oral therapeutic option for COVID-19.

Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for Severe Acute Respiratory Syndrome Coronavirus 2 3CL Protease.
Yuya Hirose, Naoya Shindo, Makiko Mori, Satsuki Onitsuka, Hikaru Isogai, Rui Hamada, Tadanari Hiramoto, Jinta Ochi, Daisuke Takahashi, Tadashi Ueda, Jose M M Caaveiro, Yuya Yoshida, Shigehiro Ohdo, Naoya Matsunaga, Shinsuke Toba, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Akihiko Sato, Eiji Kawanishi, Akio Ojida
Journal of medicinal chemistry, 65, 20, 13852, 13865, 27 Oct. 2022, [International Magazine]
English, Scientific journal, The coronavirus disease 2019 (COVID-19) pandemic has necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report a new class of covalent inhibitors of 3CLpro that possess chlorofluoroacetamide (CFA) as a cysteine-reactive warhead. Based on an aza-peptide scaffold, we synthesized a series of CFA derivatives in enantiopure form and evaluated their biochemical efficiency. The data revealed that 8a (YH-6) with the R configuration at the CFA unit strongly blocks SARS-CoV-2 replication in infected cells, and its potency is comparable to that of nirmatrelvir. X-ray structural analysis showed that YH-6 formed a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and favorable pharmacokinetic properties of YH-6 suggest its potential as a lead compound for the treatment of COVID-19.

Quantitative Analysis of Extracellular Vesicle Uptake and Fusion with Recipient Cells.
Hisaaki Hirose, Yusuke Hirai, Michihito Sasaki, Hirofumi Sawa, Shiroh Futaki
Bioconjugate chemistry, 33, 10, 1852, 1859, 19 Oct. 2022, [International Magazine]
English, Scientific journal, In precision medicine, extracellular vesicles (EVs) are promising intracellular drug delivery vehicles. The development of a quantitative analysis approach will provide valuable information from the perspective of cell biology and system design for drug delivery. Previous studies have reported quantitative methods to analyze the relative uptake or fusion of EVs to recipient cells. However, relatively few methods have enabled the simultaneous evaluation of the "number" of EVs taken up by recipient cells and those that fuse with cellular membranes. In this study, we report a simple quantitative method based on the NanoBiT system to quantify the uptake and fusion of small and large EVs (sEVs and lEVs, respectively). We assessed the abundance of these two subtypes of EVs and determined that lEVs may be more effective vehicles for transporting cargo to recipient cells. The results also indicated that both sEVs and lEVs have very low fusogenic activity, which can be improved in the presence of a fusogenic protein.

Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses.
Shun Saito, Kayo Funayama, Wataru Kato, Mayu Okuda, Meiko Kawamoto, Teruhiko Matsubara, Toshinori Sato, Akihiko Sato, Satoko Otsuguro, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Katsumi Maenaka, Kazutoshi Shindo, Masaya Imoto, Midori A Arai
Journal of natural products, 85, 11, 2583, 2591, 12 Oct. 2022, [International Magazine]
English, Scientific journal, Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a "heat shock metabolite (HSM)" by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50 concentrations.

Identification of cap-dependent endonuclease inhibitors with broad-spectrum activity against bunyaviruses.
Shinsuke Toba, Akihiko Sato, Makoto Kawai, Yoshiyuki Taoda, Yuto Unoh, Shinji Kusakabe, Haruaki Nobori, Shota Uehara, Kentaro Uemura, Keiichi Taniguchi, Masanori Kobayashi, Takeshi Noshi, Ryu Yoshida, Akira Naito, Takao Shishido, Junki Maruyama, Slobodan Paessler, Michael J Carr, William W Hall, Kumiko Yoshimatsu, Jiro Arikawa, Keita Matsuno, Yoshihiro Sakoda, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Hiroshi Kida
Proceedings of the National Academy of Sciences of the United States of America, 119, 36, e2206104119, 06 Sep. 2022, [International Magazine]
English, Scientific journal, Viral hemorrhagic fevers caused by members of the order Bunyavirales comprise endemic and emerging human infections that are significant public health concerns. Despite the disease severity, there are few therapeutic options available, and therefore effective antiviral drugs are urgently needed to reduce disease burdens. Bunyaviruses, like influenza viruses (IFVs), possess a cap-dependent endonuclease (CEN) that mediates the critical cap-snatching step of viral RNA transcription. We screened compounds from our CEN inhibitor (CENi) library and identified specific structural compounds that are 100 to 1,000 times more active in vitro than ribavirin against bunyaviruses, including Lassa virus, lymphocytic choriomeningitis virus (LCMV), and Junin virus. To investigate their inhibitory mechanism of action, drug-resistant viruses were selected in culture. Whole-genome sequencing revealed that amino acid substitutions in the CEN region of drug-resistant viruses were located in similar positions as those of the CEN α3-helix loop of IFVs derived under drug selection. Thus, our studies suggest that CENi compounds inhibit both bunyavirus and IFV replication in a mechanistically similar manner. Structural analysis revealed that the side chain of the carboxyl group at the seventh position of the main structure of the compound was essential for the high antiviral activity against bunyaviruses. In LCMV-infected mice, the compounds significantly decreased blood viral load, suppressed symptoms such as thrombocytopenia and hepatic dysfunction, and improved survival rates. These data suggest a potential broad-spectrum clinical utility of CENis for the treatment of both severe influenza and hemorrhagic diseases caused by bunyaviruses.

3種のヤブカ体内において選択されたジカウイルスのゲノム変異評価　　　　　　　　　　　　　　　
下岡 誠, 三木 要, 江下 優樹, 大場 靖子, 澤 洋文, 村松 康和, 内田 玲麻
日本獣医学会学術集会講演要旨集, 165回, [F1P, 06], (公社)日本獣医学会, Sep. 2022
Japanese

ザンビアのコウモリにおけるネルソンベイオルソレオウイルスの保有調査および分離ウイルスの病原性比較解析　　　　　　　　　　　　　　　
播磨 勇人, 佐々木 道仁, 大場 靖子, 邱 永晋, Changula Katendi, 梶原 将大, Simulundu Edgar, 谷口 怜, 高田 礼人, 西條 政幸, Hang'ombe Bernard M., 澤 洋文
日本獣医学会学術集会講演要旨集, 165回, [F1P, 09], (公社)日本獣医学会, Sep. 2022
Japanese

Genomic Surveillance of SARS-CoV-2 in the Southern Province of Zambia: Detection and Characterization of Alpha, Beta, Delta, and Omicron Variants of Concern.
Ben Katowa, Annie Kalonda, Benjamin Mubemba, Japhet Matoba, Doreen Mainza Shempela, Jay Sikalima, Boniface Kabungo, Katendi Changula, Simbarashe Chitanga, Mpanga Kasonde, Otridah Kapona, Nathan Kapata, Kunda Musonda, Mwaka Monze, John Tembo, Matthew Bates, Alimuddin Zumla, Catherine G Sutcliffe, Masahiro Kajihara, Junya Yamagishi, Ayato Takada, Hirofumi Sawa, Roma Chilengi, Victor Mukonka, Walter Muleya, Edgar Simulundu
Viruses, 14, 9, 24 Aug. 2022, [International Magazine]
English, Scientific journal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have significantly impacted the global epidemiology of the pandemic. From December 2020 to April 2022, we conducted genomic surveillance of SARS-CoV-2 in the Southern Province of Zambia, a region that shares international borders with Botswana, Namibia, and Zimbabwe and is a major tourist destination. Genetic analysis of 40 SARS-CoV-2 whole genomes revealed the circulation of Alpha (B.1.1.7), Beta (B.1.351), Delta (AY.116), and multiple Omicron subvariants with the BA.1 subvariant being predominant. Whereas Beta, Delta, and Omicron variants were associated with the second, third, and fourth pandemic waves, respectively, the Alpha variant was not associated with any wave in the country. Phylogenetic analysis showed evidence of local transmission and possible multiple introductions of SARS-CoV-2 VOCs in Zambia from different European and African countries. Across the 40 genomes analysed, a total of 292 mutations were observed, including 182 missense mutations, 66 synonymous mutations, 23 deletions, 9 insertions, 1 stop codon, and 11 mutations in the non-coding region. This study stresses the need for the continued monitoring of SARS-CoV-2 circulation in Zambia, particularly in strategically positioned regions such as the Southern Province which could be at increased risk of introduction of novel VOCs.

Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2
Ryo Takeda, Hirofumi Sawa, Michihito Sasaki, Yasuko Orba, Nako Maishi, Takuya Tsumita, Natsumi Ushijima, Yasuhiro Hida, Hidehiko Sano, Yoshimasa Kitagawa, Kyoko Hida
Scientific Reports, 12, 1, 14050, 14050, Springer Science and Business Media LLC, 18 Aug. 2022, [International Magazine]
English, Scientific journal, Abstract

Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which is present in mouthwash, is effective against bacteria, fungi, and enveloped viruses. This study was conducted to explore the antiviral effect of CPC on SARS-CoV-2. There are few reports on the effect of CPC against wild-type SARS-CoV-2 at low concentrations such as 0.001%–0.005% (10–50 µg/mL). Interestingly, we found that low concentrations of CPC suppressed the infectivity of human isolated SARS-CoV-2 strains (Wuhan, Alpha, Beta, and Gamma) even in saliva. Furthermore, we demonstrated that CPC shows anti-SARS-CoV-2 effects without disrupting the virus envelope, using sucrose density analysis and electron microscopic examination. In conclusion, this study provided experimental evidence that CPC may inhibit SARS-CoV-2 infection even at lower concentrations.

Isolation and characterization of an orthoreovirus from Indonesian fruit bats.
Kittiya Intaruck, Yukari Itakura, Mai Kishimoto, Herman M Chambaro, Agus Setiyono, Ekowati Handharyani, Kentaro Uemura, Hayato Harima, Satoshi Taniguchi, Masayuki Saijo, Takashi Kimura, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
Virology, 575, 10, 19, 15 Aug. 2022, [International Magazine]
English, Scientific journal, Nelson Bay orthoreovirus (NBV) is an emerging bat-borne virus and causes respiratory tract infections in humans sporadically. Over the last two decades, several strains genetically related to NBV were isolated from humans and various bat species, predominantly in Southeast Asia (SEA), suggesting a high prevalence of the NBV species in this region. In this study, an orthoreovirus (ORV) belonging to the NBV species was isolated from Indonesian fruit bats' feces, tentatively named Paguyaman orthoreovirus (PgORV). Serological studies revealed that 81.2% (108/133) of Indonesian fruit bats sera had neutralizing antibodies against PgORV. Whole-genome sequencing and phylogenetic analysis of PgORV suggested the occurrence of past reassortments with other NBV strains isolated in SEA, indicating the dispersal and circulation of NBV species among bats in this region. Intranasal PgORV inoculation of laboratory mice caused severe pneumonia. Our study characterized PgORV's unique genetic background and highlighted the potential risk of PgORV-related diseases in Indonesia.

Serological characterization of lineage II insect-specific flaviviruses compared with pathogenic mosquito-borne flaviviruses.
Koshiro Tabata, Yukari Itakura, Shinsuke Toba, Kentaro Uemura, Mai Kishimoto, Michihito Sasaki, Jessica J Harrison, Akihiko Sato, William W Hall, Roy A Hall, Hirofumi Sawa, Yasuko Orba
Biochemical and biophysical research communications, 616, 115, 121, 06 Aug. 2022, [International Magazine]
English, Scientific journal, The genus Flavivirus includes pathogenic tick- and mosquito-borne flaviviruses as well as non-pathogenic insect-specific flaviviruses (ISFVs). Phylogenetic analysis based on whole amino acid sequences has indicated that lineage II ISFVs have similarities to pathogenic flaviviruses. In this study, we used reactive analysis with immune serum against Psorophora flavivirus (PSFV) as a lineage IIa ISFV, and Barkeji virus (BJV) as a lineage IIb ISFV, to evaluate the antigenic similarity among lineage IIa and IIb ISFVs, and pathogenic mosquito-borne flaviviruses (MBFVs). Binding and antibody-dependent enhancement assays showed that anti-PSFV sera had broad cross-reactivity with MBFV antigens, while anti-BJV sera had low cross-reactivity. Both of the lineage II ISFV antisera were rarely observed to neutralize MBFVs. These results suggest that lineage IIa ISFV PSFV has more antigenic similarity to MBFVs than lineage IIb ISFV BJV.

A high-affinity aptamer with base-appended base-modified DNA bound to isolated authentic SARS-CoV-2 strains wild-type and B.1.617.2 (delta variant).
Hirotaka Minagawa, Hirofumi Sawa, Tomoko Fujita, Shintaro Kato, Asumi Inaguma, Miwako Hirose, Yasuko Orba, Michihito Sasaki, Koshiro Tabata, Naoki Nomura, Masashi Shingai, Yasuhiko Suzuki, Katsunori Horii
Biochemical and biophysical research communications, 614, 207, 212, 23 Jul. 2022, [International Magazine]
English, Scientific journal, Simple, highly sensitive detection technologies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial for the effective implementation of public health policies. We used the systematic evolution of ligands by exponential enrichment with a modified DNA library, including a base-appended base (uracil with a guanine base at its fifth position), to create an aptamer with a high affinity for the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. The aptamer had a dissociation constant of 1.2 and < 1 nM for the RBD and spike trimer, respectively. Furthermore, enzyme-linked aptamer assays confirmed that the aptamer binds to isolated authentic SARS-CoV-2 wild-type and B.1.617.2 (delta variant). The binding signal was larger that of commercially available anti-SARS-CoV-2 RBD antibody. Thus, this aptamer as a sensing element will enable the highly sensitive detection of SARS-CoV-2.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.
Daichi Yamasoba, Izumi Kimura, Hesham Nasser, Yuhei Morioka, Naganori Nao, Jumpei Ito, Keiya Uriu, Masumi Tsuda, Jiri Zahradnik, Kotaro Shirakawa, Rigel Suzuki, Mai Kishimoto, Yusuke Kosugi, Kouji Kobiyama, Teppei Hara, Mako Toyoda, Yuri L Tanaka, Erika P Butlertanaka, Ryo Shimizu, Hayato Ito, Lei Wang, Yoshitaka Oda, Yasuko Orba, Michihito Sasaki, Kayoko Nagata, Kumiko Yoshimatsu, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Jin Kuramochi, Motoaki Seki, Ryoji Fujiki, Atsushi Kaneda, Tadanaga Shimada, Taka-Aki Nakada, Seiichiro Sakao, Takuji Suzuki, Takamasa Ueno, Akifumi Takaori-Kondo, Ken J Ishii, Gideon Schreiber, Hirofumi Sawa, Akatsuki Saito, Takashi Irie, Shinya Tanaka, Keita Matsuno, Takasuke Fukuhara, Terumasa Ikeda, Kei Sato
Cell, 185, 12, 2103, 2115, 09 Jun. 2022, [International Magazine]
English, Scientific journal, Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.

An unusually long Rift valley fever inter-epizootic period in Zambia: Evidence for enzootic virus circulation and risk for disease outbreak.
Herman M Chambaro, Kazuyo Hirose, Michihito Sasaki, Brigadier Libanda, Yona Sinkala, Paul Fandamu, Walter Muleya, Fredrick Banda, Joseph Chizimu, David Squarre, Misheck Shawa, Yongjin Qiu, Hayato Harima, Yuki Eshita, Edgar Simulundu, Hirofumi Sawa, Yasuko Orba
PLoS neglected tropical diseases, 16, 6, e0010420, Jun. 2022, [International Magazine]
English, Scientific journal, Rift valley fever (RVF) is a mosquito-borne disease of animals and humans. Although RVF outbreaks are usually reported at 5-15-year intervals in sub-Saharan Africa, Zambia has experienced an unusually long inter-epizootic/-epidemic period of more than three decades. However, serological evidence of RVF virus (RVFV) infection in domestic ruminants during this period underscores the need for comprehensive investigation of the mechanisms of virus perpetuation and disease emergence. Mosquitoes (n = 16,778) captured from eight of the ten provinces of Zambia between April 2014 and May 2019 were pooled (n = 961) and screened for RVFV genome by a pan-phlebo RT-PCR assay. Aedes mosquito pools (n = 85) were further screened by nested RT-PCR assay. Sera from sheep (n = 13), goats (n = 259) and wild ungulates (n = 285) were screened for RVFV antibodies by ELISA while genome detection in pooled sera (n = 276) from domestic (n = 248) and wild ungulates (n = 37) was performed by real-time RT-PCR assay. To examine the association between the long inter-epizootic period and climatic variables, we examined El Niño-Southern Oscillation indices, precipitation anomalies, and normalized difference vegetation index. We then derived RVF risk maps by exploring climatic variables that would favor emergence of primary RVFV vectors. While no RVFV genome could be detected in pooled mosquito and serum samples, seroprevalence was significantly high (OR = 8.13, 95% CI [4.63-14.25]) in wild ungulates (33.7%; 96/285) compared to domestic ruminants (5.6%; 16/272). Retrospective analysis of RVF epizootics in Zambia showed a positive correlation between anomalous precipitation (La Niña) and disease emergence. On risk mapping, whilst northern and eastern parts of the country were at high risk, domestic ruminant population density was low (< 21 animals/km2) in these areas compared to low risk areas (>21 animals/km2). Besides evidence of silent circulation of RVFV and the risk of disease emergence in some areas, wildlife may play a role in the maintenance of RVFV in Zambia.

Detection of Tick-Borne Bacterial and Protozoan Pathogens in Ticks from the Zambia-Angola Border.
Yongjin Qiu, Martin Simuunza, Masahiro Kajihara, Joseph Ndebe, Ngonda Saasa, Penjani Kapila, Hayato Furumoto, Alice C C Lau, Ryo Nakao, Ayato Takada, Hirofumi Sawa
Pathogens (Basel, Switzerland), 11, 5, 10 May 2022, [International Magazine]
English, Scientific journal, Tick-borne diseases (TBDs), including emerging and re-emerging zoonoses, are of public health importance worldwide; however, TBDs tend to be overlooked, especially in countries with fewer resources, such as Zambia and Angola. Here, we investigated Rickettsia, Anaplasmataceae, and Apicomplexan pathogens in 59 and 96 adult ticks collected from dogs and cattle, respectively, in Shangombo, a town at the Zambia-Angola border. We detected Richkettsia africae and Rickettsia aeschilimannii in 15.6% of Amblyomma variegatum and 41.7% of Hyalomma truncatum ticks, respectively. Ehrlichia minasensis was detected in 18.8% of H. truncatum, and Candidatus Midichloria mitochondrii was determined in Hyalomma marginatum. We also detected Babesia caballi and Theileria velifera in A. variegatum ticks with a 4.4% and 6.7% prevalence, respectively. In addition, Hepatozoon canis was detected in 6.5% of Rhipicephalus lunulatus and 4.3% of Rhipicephalus sanguineus. Coinfection of R. aeshilimannii and E. minasensis were observed in 4.2% of H. truncatum. This is the first report of Ca. M. mitochondrii and E. minasensis, and the second report of B. caballi, in the country. Rickettsia africae and R. aeschlimannii are pathogenic to humans, and E. minasensis, B. caballi, T. velifera, and H. canis are pathogenic to animals. Therefore, individuals, clinicians, veterinarians, and pet owners should be aware of the distribution of these pathogens in the area.

Glu333 in rabies virus glycoprotein is involved in virus attenuation through astrocyte infection and interferon responses.
Yukari Itakura, Koshiro Tabata, Kohei Morimoto, Naoto Ito, Herman M Chambaro, Ryota Eguchi, Ken-Ichi Otsuguro, William W Hall, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
iScience, 25, 4, 104122, 104122, 15 Apr. 2022, [International Magazine]
English, Scientific journal, The amino acid residue at position 333 of the rabies virus (RABV) glycoprotein (G333) is a major determinant of RABV pathogenicity. Virulent RABV strains possess Arg333, whereas the attenuated strain HEP-Flury (HEP) possesses Glu333. To investigate the potential attenuation mechanism dependent on a single amino acid at G333, comparative analysis was performed between HEP and HEP333R mutant with Arg333. We examined their respective tropism for astrocytes and the subsequent immune responses in astrocytes. Virus replication and subsequent interferon (IFN) responses in astrocytes infected with HEP were increased compared with HEP333R both in vitro and in vivo. Furthermore, involvement of IFN in the avirulency of HEP was demonstrated in IFN-receptor knockout mice. These results indicate that Glu333 contributes to RABV attenuation by determining the ability of the virus to infect astrocytes and stimulate subsequent IFN responses.

Autochthonous Leishmania infantum in Dogs, Zambia, 2021.
David Squarre, Herman M Chambaro, Kyoko Hayashida, Lavel C Moonga, Yongjin Qiu, Yasuyuki Goto, Elizabeth Oparaocha, Chisoni Mumba, Walter Muleya, Patricia Bwalya, Joseph Chizimu, Mwelwa Chembensofu, Edgar Simulundu, Wizaso Mwasinga, Nelly Banda, Racheal Mwenda, Junya Yamagishi, King S Nalubamba, Fredrick Banda, Musso Munyeme, Hirofumi Sawa, Paul Fandamu
Emerging infectious diseases, 28, 4, 888, 890, Apr. 2022, [International Magazine]
English, Scientific journal, Leishmaniases are neglected tropical diseases of humans and animals. We detected Leishmania infantum in 3 mixed-breed dogs in Zambia that had no travel history outside the country. Our findings suggest presence of and probable emergence of leishmaniasis in Zambia, indicating the need for physicians and veterinarians to consider the disease during diagnosis.

Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19.
Yuto Unoh, Shota Uehara, Kenji Nakahara, Haruaki Nobori, Yukiko Yamatsu, Shiho Yamamoto, Yuki Maruyama, Yoshiyuki Taoda, Koji Kasamatsu, Takahiro Suto, Kensuke Kouki, Atsufumi Nakahashi, Sho Kawashima, Takao Sanaki, Shinsuke Toba, Kentaro Uemura, Tohru Mizutare, Shigeru Ando, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Akihiko Sato, Takafumi Sato, Teruhisa Kato, Yuki Tachibana
Journal of medicinal chemistry, 65, 9, 6499, 6512, 30 Mar. 2022, [International Magazine]
English, Scientific journal, The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths and threatens public health and safety. Despite the rapid global spread of COVID-19 vaccines, effective oral antiviral drugs are urgently needed. Here, we describe the discovery of S-217622, the first oral noncovalent, nonpeptidic SARS-CoV-2 3CL protease inhibitor clinical candidate. S-217622 was discovered via virtual screening followed by biological screening of an in-house compound library, and optimization of the hit compound using a structure-based drug design strategy. S-217622 exhibited antiviral activity in vitro against current outbreaking SARS-CoV-2 variants and showed favorable pharmacokinetic profiles in vivo for once-daily oral dosing. Furthermore, S-217622 dose-dependently inhibited intrapulmonary replication of SARS-CoV-2 in mice, indicating that this novel noncovalent inhibitor could be a potential oral agent for treating COVID-19.

SARS-COV-2感染マウスを用いた肺の病理学的解析　　　　　　　　　　　　　　　
水野 天音, 積田 卓也, 武田 遼, 澤 洋文, 佐々木 道仁, 鳥羽 晋輔, 田中 宏典, 任 子驍, 樋田 泰浩, 樋田 京子
日本病理学会会誌, 111, 1, 348, 348, (一社)日本病理学会, Mar. 2022
Japanese

マウス感染モデルを用いたCOVID-19重症化における血管病態の解析
積田 卓也, 武田 遼, 澤 洋文, 佐々木 道仁, 間石 奈湖, 樋田 泰浩, 松田 彩, 佐藤 彰彦, 鳥羽 晋輔, 田中 宏典, 樋田 京子
日本内分泌学会雑誌, 97, 5, 1514, 1514, (一社)日本内分泌学会, Mar. 2022
Japanese

Application of Acoustic Ejection MS System to High-Throughput Screening for SARS-CoV-2 3CL Protease Inhibitors.
Tsukasa Hasegawa, Riyo M Imamura, Tateki Suzuki, Takao Hashiguchi, Takao Nomura, Satoko Otsuguro, Katsumi Maenaka, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Akihiko Sato, Takayoshi Okabe, Tetsuo Nagano, Hirotatsu Kojima
Chemical & pharmaceutical bulletin, 70, 3, 199, 201, 01 Mar. 2022, [Domestic magazines]
English, Scientific journal, MS is a powerful methodology for chemical screening to directly quantify substrates and products of enzymes, but its low throughput has been an issue. Recently, an acoustic liquid-handling apparatus (Echo®) used for rapid nano-dispensing has been coupled to a high-sensitivity mass spectrometer to create the Echo® MS system, and we applied this system to screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease inhibitors. Primary screening of 32033 chemical samples was completed in 12 h. Among the hits showing selective, dose-dependent 3CL-inhibitory activity, 8 compounds showed antiviral activity in cell-based assay.

Synthesis and Anti-dengue Virus Activity of 5-Ethynylimidazole-4-carboxamide (EICA) Nucleotide Prodrugs.
Motoki Nakamura, Kentaro Uemura, Noriko Saito-Tarashima, Akihiko Sato, Yasuko Orba, Hirofumi Sawa, Akira Matsuda, Katsumi Maenaka, Noriaki Minakawa
Chemical & pharmaceutical bulletin, 70, 3, 220, 225, 01 Mar. 2022, [Domestic magazines]
English, Scientific journal, We previously showed that 5-ethynyl-(1-β-D-ribofuranosyl)imidazole-4-carboxamide (1; EICAR) is a potent anti-dengue virus (DENV) compound but is cytotoxic to some cell lines, while its 4-thio derivative, 5-ethynyl-(4-thio-1-β-D-ribofuranosyl)imidazole-4-carboxamide (2; 4'-thioEICAR), has less cytotoxicity but also less anti-DENV activity. Based on the hypothesis that the lower anti-DENV activity of 2 is due to reduced susceptibility to phosphorylation by cellular kinase(s), we investigated whether a monophosphate prodrug of 2 can improve its activity. Here, we first prepared two types of prodrug of 1, which revealed that the S-acyl-2-thioethyl (SATE) prodrug had stronger anti-DENV activity than the aryloxyphosphoramidate (so-called ProTide) prodrug. Based on these findings, we next prepared the SATE prodrug of 4'-thioEICAR 18. As expected, the resulting 18 showed potent anti-DENV activity, which was comparable to that of 1; however, its cytotoxicity was also increased relative to 2. Our findings suggest that prodrugs of 4'-thioribonucleoside derivatives such as EICAR (1) represent an effective approach to developing potent biologically active compounds; however, the balance between antiviral activity and cytotoxicity remains to be addressed.

Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant.
Rigel Suzuki, Daichi Yamasoba, Izumi Kimura, Lei Wang, Mai Kishimoto, Jumpei Ito, Yuhei Morioka, Naganori Nao, Hesham Nasser, Keiya Uriu, Yusuke Kosugi, Masumi Tsuda, Yasuko Orba, Michihito Sasaki, Ryo Shimizu, Ryoko Kawabata, Kumiko Yoshimatsu, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Hirofumi Sawa, Terumasa Ikeda, Takashi Irie, Keita Matsuno, Shinya Tanaka, Takasuke Fukuhara, Kei Sato
Nature, 603, 7902, 700, 705, Mar. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern1. In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell-cell fusion2,3, the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.

Current knowledge of vector-borne zoonotic pathogens in Zambia: A clarion call to scaling-up "One Health" research in the wake of emerging and re-emerging infectious diseases.
Benjamin Mubemba, Monicah M Mburu, Katendi Changula, Walter Muleya, Lavel C Moonga, Herman M Chambaro, Masahiro Kajihara, Yongjin Qiu, Yasuko Orba, Kyoko Hayashida, Catherine G Sutcliffe, Douglas E Norris, Philip E Thuma, Phillimon Ndubani, Simbarashe Chitanga, Hirofumi Sawa, Ayato Takada, Edgar Simulundu
PLoS neglected tropical diseases, 16, 2, e0010193, Feb. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Although vector-borne zoonotic diseases are a major public health threat globally, they are usually neglected, especially among resource-constrained countries, including those in sub-Saharan Africa. This scoping review examined the current knowledge and identified research gaps of vector-borne zoonotic pathogens in Zambia. METHODS AND FINDINGS: Major scientific databases (Web of Science, PubMed, Scopus, Google Scholar, CABI, Scientific Information Database (SID)) were searched for articles describing vector-borne (mosquitoes, ticks, fleas and tsetse flies) zoonotic pathogens in Zambia. Several mosquito-borne arboviruses have been reported including Yellow fever, Ntaya, Mayaro, Dengue, Zika, West Nile, Chikungunya, Sindbis, and Rift Valley fever viruses. Flea-borne zoonotic pathogens reported include Yersinia pestis and Rickettsia felis. Trypanosoma sp. was the only tsetse fly-borne pathogen identified. Further, tick-borne zoonotic pathogens reported included Crimean-Congo Haemorrhagic fever virus, Rickettsia sp., Anaplasma sp., Ehrlichia sp., Borrelia sp., and Coxiella burnetii. CONCLUSIONS: This study revealed the presence of many vector-borne zoonotic pathogens circulating in vectors and animals in Zambia. Though reports of human clinical cases were limited, several serological studies provided considerable evidence of zoonotic transmission of vector-borne pathogens in humans. However, the disease burden in humans attributable to vector-borne zoonotic infections could not be ascertained from the available reports and this precludes the formulation of national policies that could help in the control and mitigation of the impact of these diseases in Zambia. Therefore, there is an urgent need to scale-up "One Health" research in emerging and re-emerging infectious diseases to enable the country to prepare for future epidemics, including pandemics.

Seroprevalence and Risk Factors of Crimean-Congo Hemorrhagic Fever in Cattle of Smallholder Farmers in Central Malawi.
Marvin Collen Phonera, Martin Chitolongo Simuunza, Henson Kainga, Joseph Ndebe, Mwelwa Chembensofu, Elisha Chatanga, Setiala Kanyanda, Katendi Changula, Walter Muleya, Benjamin Mubemba, Simbarashe Chitanga, Masahiro Kajihara, Hirofumi Sawa, Gilson Njunga, Ayato Takada, Edgar Simulundu
Pathogens (Basel, Switzerland), 10, 12, 10 Dec. 2021, [International Magazine]
English, Scientific journal, Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Africa, Asia, and Eastern Europe where it circulates among animals and ticks causing sporadic outbreaks in humans. Although CCHF is endemic in sub-Saharan Africa, epidemiological information is lacking in many countries, including Malawi. To assess the risk of CCHF in Malawi, we conducted an epidemiological study in cattle reared by smallholder livestock farmers in central Malawi. A cross-sectional study was conducted in April 2020 involving seven districts, four from Kasungu and three from Lilongwe Agriculture Development Divisions. A structured questionnaire was administered to farmers to obtain demographic, animal management, and ecological risk factors data. Sera were collected from randomly selected cattle and screened for CCHF virus (CCHFV) specific antibodies using a commercial ELISA kit. Ticks were collected from cattle and classified morphologically to species level. An overall CCHFV seropositivity rate of 46.9% (n = 416; 95% CI: 42.0-51.8%) was observed. The seropositivity was significantly associated with the age of cattle (p < 0.001), sex (p < 0.001), presence of ticks in herds (p = 0.01), district (p = 0.025), and type of grazing lands (p = 0.013). Five species of ticks were identified, including Hyalomma truncatum, a known vector of CCHFV. Ticks of the species Hyalomma truncatum were not detected in two districts with the highest seroprevalence for CCHF and vector competency must be further explored in the study area. To our knowledge, this is the first report of serologic evidence of the presence of CCHV among smallholder cattle in central Malawi. This study emphasizes the need for continued monitoring of CCHFV infection among livestock, ticks, and humans for the development of data-based risk mitigation strategies.

Influenza A and D Viruses in Non-Human Mammalian Hosts in Africa: A Systematic Review and Meta-Analysis.
Annie Kalonda, Marvin Phonera, Ngonda Saasa, Masahiro Kajihara, Catherine G Sutcliffe, Hirofumi Sawa, Ayato Takada, Edgar Simulundu
Viruses, 13, 12, 02 Dec. 2021, [International Magazine]
English, Scientific journal, We conducted a systematic review and meta-analysis to investigate the prevalence and current knowledge of influenza A virus (IAV) and influenza D virus (IDV) in non-human mammalian hosts in Africa. PubMed, Google Scholar, Wiley Online Library and World Organisation for Animal Health (OIE-WAHIS) were searched for studies on IAV and IDV from 2000 to 2020. Pooled prevalence and seroprevalences were estimated using the quality effects meta-analysis model. The estimated pooled prevalence and seroprevalence of IAV in pigs in Africa was 1.6% (95% CI: 0-5%) and 14.9% (95% CI: 5-28%), respectively. The seroprevalence of IDV was 87.2% (95% CI: 24-100%) in camels, 9.3% (95% CI: 0-24%) in cattle, 2.2% (95% CI: 0-4%) in small ruminants and 0.0% (95% CI: 0-2%) in pigs. In pigs, H1N1 and H1N1pdm09 IAVs were commonly detected. Notably, the highly pathogenic H5N1 virus was also detected in pigs. Other subtypes detected serologically and/or virologically included H3N8 and H7N7 in equids, H1N1, and H3N8 and H5N1 in dogs and cats. Furthermore, various wildlife animals were exposed to different IAV subtypes. For prudent mitigation of influenza epizootics and possible human infections, influenza surveillance efforts in Africa should not neglect non-human mammalian hosts. The impact of IAV and IDV in non-human mammalian hosts in Africa deserves further investigation.

Hepatitis E virus infection in pigs: a first report from Zambia.
Herman M Chambaro, Michihito Sasaki, Walter Muleya, Masahiro Kajihara, Misheck Shawa, Kabemba E Mwape, Hayato Harima, Yongjin Qiu, William W Hall, Paul Fandamu, David Squarre, Edgar Simulundu, Hirofumi Sawa, Yasuko Orba
Emerging microbes & infections, 10, 1, 2169, 2172, Dec. 2021, [International Magazine]
English, While evidence suggests presence of HEV infection in humans in Zambia, currently, there is no information on its occurrence in domestic pigs. Here, we investigated the presence of HEV antibodies and genome in domestic pigs in Zambia. Sera (n = 484) from domestic pigs were screened for antibodies against HEV by ELISA while genome detection in fecal (n = 25) and liver (n = 100) samples from slaughter pigs was conducted using nested RT-PCR assay. Overall, seroprevalence was 47.7% (231/484) while zoonotic genotype 3 HEV RNA was detected in 16.0% (20/125) of slaughtered pigs. This is the first report to highlight occurrence of HEV infection in domestic pigs in Zambia. This finding suggests possible contamination of the pork supply chain. Moreover, there is a potential risk of zoonotic transmission of HEV to abattoir workers, pig farmers and handlers.

SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis
Ji-Seung Yoo, Michihito Sasaki, Steven X. Cho, Yusuke Kasuga, Baohui Zhu, Ryota Ouda, Yasuko Orba, Paul de Figueiredo, Hirofumi Sawa, Koichi S. Kobayashi
Nature Communications, 12, 1, 6602, 6602, Springer Science and Business Media LLC, Dec. 2021, [International Magazine]
English, Scientific journal, The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5.

Evidence of Borrelia theileri in Wild and Domestic Animals in the Kafue Ecosystem of Zambia.
Yongjin Qiu, David Squarre, Yukiko Nakamura, Alice C C Lau, Lavel Chinyama Moonga, Naoko Kawai, Aiko Ohnuma, Kyoko Hayashida, Ryo Nakao, Junya Yamagishi, Hirofumi Sawa, Boniface Namangala, Hiroki Kawabata
Microorganisms, 9, 11, 22 Nov. 2021, [International Magazine]
English, Scientific journal, Members of the genus Borrelia are arthropod-borne spirochetes that are human and animal pathogens. Vertebrate hosts, including wild animals, are pivotal to the circulation and maintenance of Borrelia spirochetes. However, information on Borrelia spirochetes in vertebrate hosts in Zambia is limited. Thus, we aimed to investigate the presence of Borrelia spirochetes in wild animals and cattle in Zambia. A total of 140 wild animals of four species and 488 cattle DNA samples from /near the Kafue National Park were collected for real-time PCR screening, followed by characterization using three different genes with positive samples. Five impalas and 20 cattle tested positive using real-time PCR, and sequence analysis revealed that the detected Borrelia were identified to be Borrelia theileri, a causative agent of bovine borreliosis. This is the first evidence of Borrelia theileri in African wildlife and cattle in Zambia. Our results suggest that clinical differentiation between bovine borreliosis and other bovine diseases endemic in Zambia is required for better treatment and control measures. As this study only included wild and domestic animals in the Kafue ecosystem, further investigations in other areas and with more wildlife and livestock species are needed to clarify a comprehensive epidemiological status of Borrelia theileri in Zambia.

Air-liquid interphase culture confers SARS-CoV-2 susceptibility to A549 alveolar epithelial cells.
Michihito Sasaki, Mai Kishimoto, Yukari Itakura, Koshiro Tabata, Kittiya Intaruck, Kentaro Uemura, Shinsuke Toba, Takao Sanaki, Akihiko Sato, William W Hall, Yasuko Orba, Hirofumi Sawa
Biochemical and biophysical research communications, 577, 146, 151, 05 Nov. 2021, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, The human lung cell A549 is susceptible to infection with a number of respiratory viruses. However, A549 cells are resistant to Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection in conventional submerged culture, and this would appear to be due to low expression levels of the SARS-CoV-2 entry receptor: angiotensin-converting enzyme-2 (ACE2). Here, we examined SARS-CoV-2 susceptibility to A549 cells after adaptation to air-liquid interface (ALI) culture. A549 cells in ALI culture yielded a layer of mucus on their apical surface, exhibited decreased expression levels of the proliferation marker KI-67 and intriguingly became susceptible to SARS-CoV-2 infection. We found that A549 cells increased the endogenous expression levels of ACE2 and TMPRSS2 following adaptation to ALI culture conditions. Camostat, a TMPRSS2 inhibitor, reduced SARS-CoV-2 infection in ALI-cultured A549 cells. These findings indicate that ALI culture switches the phenotype of A549 cells from resistance to susceptibility to SARS-CoV-2 infection through upregulation of ACE2 and TMPRSS2.

細胞外小胞の受容細胞への内在化量および膜融合量の定量化技術の開発　　　　　　　　　　　　　　　
平井 勇祐, 広瀬 久昭, 佐々木 道仁, 澤 洋文, 二木 史朗
日本生化学会大会プログラム・講演要旨集, 94回, [P, 440], (公社)日本生化学会, Nov. 2021
Japanese

細胞外小胞の受容細胞への内在化量および膜融合量の定量化技術の開発　　　　　　　　　　　　　　　
平井 勇祐, 広瀬 久昭, 佐々木 道仁, 澤 洋文, 二木 史朗
日本生化学会大会プログラム・講演要旨集, 94回, [P, 440], (公社)日本生化学会, Nov. 2021
Japanese

食品成分およびその誘導体群によるコロナウイルス感染抑制効果　　　　　　　　　　　　　　　
村井 勇太, ムトマイナー, クーラス・サジール, 臼杵 靖剛, 湯山 耕平, 中岡 慎治, 佐々木 道仁, 大場 靖子, 佐藤 彰彦, 五十嵐 靖之, 澤 洋文, 門出 健次
日本生化学会大会プログラム・講演要旨集, 94回, [P, 943], (公社)日本生化学会, Nov. 2021
Japanese

Serological and molecular epidemiological study on swine influenza in Zambia.
Hayato Harima, Kosuke Okuya, Masahiro Kajihara, Hirohito Ogawa, Edgar Simulundu, Eugene Bwalya, Yongjin Qiu, Akina Mori-Kajihara, Musso Munyeme, Yoshihiro Sakoda, Takehiko Saito, Bernard M Hang'ombe, Hirofumi Sawa, Aaron S Mweene, Ayato Takada
Transboundary and emerging diseases, 69, 4, e931-e943, 01 Nov. 2021, [International Magazine]
English, Scientific journal, Influenza A viruses (IAVs) cause highly contagious respiratory diseases in humans and animals. In 2009, a swine-origin pandemic H1N1 IAV, designated A(H1N1)pdm09 virus, spread worldwide, and has since frequently been introduced into pig populations. Since novel reassortant IAVs with pandemic potential may emerge in pigs, surveillance for IAV in pigs is therefore necessary not only for the pig industry but also for public health. However, epidemiological information on IAV infection of pigs in Africa remains sparse. In this study, we collected 246 serum and 605 nasal swab samples from pigs in Zambia during the years 2011-2018. Serological analyses revealed that 49% and 32% of the sera collected in 2011 were positive for hemagglutination-inhibition (HI) and neutralizing antibodies against A(H1N1)pdm09 virus, respectively, whereas less than 5.3% of sera collected during the following period (2012-2018) were positive in both serological tests. The positive rate and the neutralization titres to A(H1N1)pdm09 virus were higher than those to classical swine H1N1 and H1N2 IAVs. On the other hand, the positive rate for swine H3N2 IAV was very low in the pig population in Zambia in 2011-2018 (5.3% and 0% in HI and neutralization tests, respectively). From nasal swab samples, we isolated one H3N2 and eight H1N1 IAV strains with an isolation rate of 1.5%. Phylogenetic analyses of all eight gene segments revealed that the isolated IAVs were closely related to human IAV strains belonging to A(H1N1)pdm09 and seasonal H3N2 lineages. Our findings indicate that reverse zoonotic transmission from humans to pigs occurred during the study period in Zambia and highlight the need for continued surveillance to monitor the status of IAVs circulating in swine populations in Africa.

Abnormal blood coagulation and kidney damage in aged hamsters infected with severe acute respiratory syndrome coronavirus 2
Marumi Ohno, Michihito Sasaki, Yasuko Orba, Toshiki Sekiya, Md Abdul Masum, Osamu Ichii, Tatsuya Sawamura, Akemi Kakino, Yasuhiko Suzuki, Hiroshi Kida, Hirofumi Sawa, Masashi Shingai
Viruses, 13, 11, Nov. 2021, [International Magazine]
English, Scientific journal

5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2.
Kentaro Uemura, Haruaki Nobori, Akihiko Sato, Takao Sanaki, Shinsuke Toba, Michihito Sasaki, Akiho Murai, Noriko Saito-Tarashima, Noriaki Minakawa, Yasuko Orba, Hiroaki Kariwa, William W Hall, Hirofumi Sawa, Akira Matsuda, Katsumi Maenaka
iScience, 24, 10, 103120, 103120, 22 Oct. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Newly emerging or re-emerging viral infections continue to cause significant morbidity and mortality every year worldwide, resulting in serious effects on both health and the global economy. Despite significant drug discovery research against dengue viruses (DENVs) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), no fully effective and specific drugs directed against these viruses have been discovered. Here, we examined the anti-DENV activity of tubercidin derivatives from a compound library from Hokkaido University and demonstrated that 5-hydroxymethyltubercidin (HMTU, HUP1108) possessed both potent anti-flavivirus and anti-coronavirus activities at submicromolar levels without significant cytotoxicity. Furthermore, HMTU inhibited viral RNA replication and specifically inhibited replication at the late stages of the SARS-CoV-2 infection process. Finally, we demonstrated that HMTU 5'-triphosphate inhibited RNA extension catalyzed by the viral RNA-dependent RNA polymerase. Our findings suggest that HMTU has the potential of serving as a lead compound for the development of a broad spectrum of antiviral agents, including SARS-CoV-2.

Rickettsia lusitaniae in Ornithodoros Porcinus Ticks, Zambia.
Simbarashe Chitanga, Herman M Chambaro, Lavel C Moonga, Kyoko Hayashida, Junya Yamagishi, Walter Muleya, Katendi Changula, Benjamin Mubemba, Manyando Simbotwe, David Squarre, Paul Fandamu, King S Nalubamba, Yongjin Qiu, Sawa Hirofumi, Edgar Simulundu
Pathogens (Basel, Switzerland), 10, 10, 12 Oct. 2021, [International Magazine]
English, Scientific journal, Rickettsial pathogens are amongst the emerging and re-emerging vector-borne zoonoses of public health importance. Though traditionally considered to be transmitted by ixodid ticks, the role of argasid ticks as vectors of these pathogens is increasingly being recognized. While bat-feeding (Ornithodoros faini) and chicken-feeding (Argas walkerae) argasid ticks have been shown to harbor Rickettsia pathogens in Zambia, there are currently no reports of Rickettsia infection in southern Africa from warthog-feeding (Phacochoerus africanus) soft ticks, particularly Ornithodoros moubata and Ornithodoros porcinus. Our study sought to expand on the existing knowledge on the role of soft ticks in the epidemiology of Rickettsia species through screening for Rickettsia pathogens in warthog burrow-dwelling soft ticks from two national parks in Zambia. The tick species from which Rickettsia were detected in this study were identified as Ornithodoros porcinus, and an overall minimal Rickettsia infection rate of 19.8% (32/162) was observed. All of the sequenced Rickettsia were identified as Rickettsia lusitaniae based on nucleotide sequence similarity and phylogenetic analysis of the citrate synthase (gltA) and 17kDa common antigen (htrA) genes. Utilizing all of the gltA (n = 10) and htrA (n = 12) nucleotide sequences obtained in this study, BLAST analysis showed 100% nucleotide similarity to Rickettsia lusitaniae. Phylogenetic analysis revealed that all of the Zambian gltA and htrA gene sequences could be grouped with those of Rickettsia lusitaniae obtained in various parts of the world. Our data suggest that Rickettsia lusitaniae has a wider geographic and vector range, enhancing to our understanding of Rickettsia lusitaniae epidemiology in sub-Saharan Africa.

A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.
Taishi Onodera, Shunsuke Kita, Yu Adachi, Saya Moriyama, Akihiko Sato, Takao Nomura, Shuhei Sakakibara, Takeshi Inoue, Takashi Tadokoro, Yuki Anraku, Kohei Yumoto, Cong Tian, Hideo Fukuhara, Michihito Sasaki, Yasuko Orba, Nozomi Shiwa, Naoko Iwata, Noriyo Nagata, Tateki Suzuki, Jiei Sasaki, Tsuyoshi Sekizuka, Keisuke Tonouchi, Lin Sun, Shuetsu Fukushi, Hiroyuki Satofuka, Yasuhiro Kazuki, Mitsuo Oshimura, Tomohiro Kurosaki, Makoto Kuroda, Yoshiharu Matsuura, Tadaki Suzuki, Hirofumi Sawa, Takao Hashiguchi, Katsumi Maenaka, Yoshimasa Takahashi
Immunity, 54, 10, 2385, 2398, 12 Oct. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.

Novel Virulent Bacteriophage ΦSG005, Which Infects Streptococcus gordonii, Forms a Distinct Clade among Streptococcus Viruses.
Jumpei Fujiki, Shin-Ichi Yoshida, Tomohiro Nakamura, Keisuke Nakamura, Yurika Amano, Keita Nishida, Keitaro Nishi, Michihito Sasaki, Tomohito Iwasaki, Hirofumi Sawa, Hitoshi Komatsuzawa, Hiroshi Hijioka, Hidetomo Iwano
Viruses, 13, 10, 29 Sep. 2021, [International Magazine]
English, Scientific journal, Bacteriophages are viruses that specifically infect bacteria and are classified as either virulent phages or temperate phages. Despite virulent phages being promising antimicrobial agents due to their bactericidal effects, the implementation of phage therapy depends on the availability of virulent phages against target bacteria. Notably, virulent phages of Streptococcus gordonii, which resides in the oral cavity and is an opportunistic pathogen that can cause periodontitis and endocarditis have previously never been found. We thus attempted to isolate virulent phages against S. gordonii. In the present study, we report for the first time a virulent bacteriophage against S. gordonii, ΦSG005, discovered from drainage water. ΦSG005 is composed of a short, non-contractile tail and a long head, revealing Podoviridae characteristics via electron microscopic analysis. In turbidity reduction assays, ΦSG005 showed efficient bactericidal effects on S. gordonii. Whole-genome sequencing showed that the virus has a DNA genome of 16,127 bp with 21 coding sequences. We identified no prophage-related elements such as integrase in the ΦSG005 genome, demonstrating that the virus is a virulent phage. Phylogenetic analysis indicated that ΦSG005 forms a distinct clade among the streptococcus viruses and is positioned next to streptococcus virus C1. Molecular characterization revealed the presence of an anti-CRISPR (Acr) IIA5-like protein in the ΦSG005 genome. These findings facilitate our understanding of streptococcus viruses and advance the development of phage therapy against S. gordonii infection.

LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19
Hideyuki Shimizu, Manabu Kodama, Masaki Matsumoto, Yasuko Orba, Michihito Sasaki, Akihiko Sato, Hirofumi Sawa, Keiichi I. Nakayama
bioRxiv, 25, 11, 105314, 105314, Cold Spring Harbor Laboratory, 25 Sep. 2021, [International Magazine]
English, Scientific journal, Although numerous promising therapeutic targets for human diseases have been discovered, most have not been successfully translated into clinical practice¹. A bottleneck in the application of basic research findings to patients is the enormous cost, time, and effort required for high-throughput screening of potential drugs² for given therapeutic targets. Recent advances in 3D docking simulations have not solved this problem, given that 3D protein structures with sufficient resolution are not always available and that they are computationally expensive to obtain. Here we have developed LIGHTHOUSE, a graph-based deep learning approach for discovery of the hidden principles underlying the association of small-molecule compounds with target proteins, and we present its validation by identifying potential therapeutic compounds for various human diseases. Without any 3D structural information for proteins or chemicals, LIGHTHOUSE estimates protein-compound scores that incorporate known evolutionary relations and available experimental data. It identified novel therapeutics for cancer, lifestyle-related disease, and bacterial infection. Moreover, LIGHTHOUSE predicted ethoxzolamide as a therapeutic for coronavirus disease 2019 (COVID-19), and this agent was indeed effective against alpha, beta, gamma, and delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are rampant worldwide. Given that ethoxzolamide is already approved for several diseases, it could be rapidly deployed for the treatment of patients with COVID-19. We envision that LIGHTHOUSE will bring about a paradigm shift in translational medicine, providing a bridge from bench side to bedside.

A targeted approach with nanopore sequencing for the universal detection and identification of flaviviruses.
Patrick Reteng, Linh Nguyen Thuy, Tam Tran Thi Minh, Maria Angélica Monteiro de Mello Mares-Guia, Maria Celeste Torres, Ana Maria Bispo de Filippis, Yasuko Orba, Shintaro Kobayashi, Kyoko Hayashida, Hirofumi Sawa, William W Hall, Lan Anh Nguyen Thi, Junya Yamagishi
Scientific reports, 11, 1, 19031, 19031, 24 Sep. 2021, [International Magazine]
English, Scientific journal, Nucleic acid test (NAT), most typically quantitative PCR, is one of the standard methods for species specific flavivirus diagnosis. Semi-comprehensive NATs such as pan-flavivirus PCR which covers genus Flavivirus are also available; however, further specification by sequencing is required for species level differentiation. In this study, a semi-comprehensive detection system that allows species differentiation of flaviviruses was developed by integration of the pan-flavivirus PCR and Nanopore sequencing. In addition, a multiplexing method was established by adding index sequences through the PCR with a streamlined bioinformatics pipeline. This enables defining cut-off values for observed read counts. In the laboratory setting, this approach allowed the detection of up to nine different flaviviruses. Using clinical samples collected in Vietnam and Brazil, seven different flaviviruses were also detected. When compared to a commercial NAT, the sensitivity and specificity of our system were 66.7% and 95.4%, respectively. Conversely, when compared to our system, the sensitivity and specificity of the commercial NAT were 57.1% and 96.9%, respectively. In addition, Nanopore sequencing detected more positive samples (n = 8) compared to the commercial NAT (n = 6). Collectively, our study has established a semi-comprehensive sequencing-based diagnostic system for the detection of flaviviruses at extremely affordable costs, considerable sensitivity, and only requires simple experimental methods.

A novel nairovirus associated with acute febrile illness in Hokkaido, Japan.
Fumihiro Kodama, Hiroki Yamaguchi, Eunsil Park, Kango Tatemoto, Mariko Sashika, Ryo Nakao, Yurino Terauchi, Keita Mizuma, Yasuko Orba, Hiroaki Kariwa, Katsuro Hagiwara, Katsunori Okazaki, Akiko Goto, Rika Komagome, Masahiro Miyoshi, Takuya Ito, Kimiaki Yamano, Kentaro Yoshii, Chiaki Funaki, Mariko Ishizuka, Asako Shigeno, Yukari Itakura, Lesley Bell-Sakyi, Shunji Edagawa, Atsushi Nagasaka, Yoshihiro Sakoda, Hirofumi Sawa, Ken Maeda, Masayuki Saijo, Keita Matsuno
Nature communications, 12, 1, 5539, 5539, 20 Sep. 2021, [International Magazine]
English, Scientific journal, The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014-2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan.

Molecular Survey of Babesia and Anaplasma Infection in Cattle in Bolivia
Shohei Ogata, Juan Antonio Cristian Pereira, Loza Vega Ariel Jhonny, Herbas Perez Gladys Carolina, Keita Matsuno, Yasuko Orba, Hirofumi Sawa, Fumihiko Kawamori, Nariaki Nonaka, Ryo Nakao
Veterinary Sciences, 8, 9, 188, 188, MDPI AG, 07 Sep. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Latin American countries produce more than a quarter of the world’s beef and are a major global supplier of livestock protein. Tick-borne diseases (TBDs) are a major constraint to the livestock industry worldwide, including in Latin America. The aim of this study was to detect and characterise tick-borne pathogens in cattle from Santa Cruz, Bolivia, where no detailed epidemiological data are available. Blood samples were collected from 104 cattle. Apicomplexan parasites were detected by nested PCR amplification of the 18S ribosomal RNA gene (rDNA), and Anaplasmataceae was screened by the PCR amplification of 16S rDNA, followed by characterisation based on the heat shock protein and citrate synthase gene sequences. Babesia infection was observed in nine cattle (one Babesia bovis and eight Babesia bigemina), while Anaplasmataceae infection was detected in thirty-two cattle. A sequencing analysis confirmed the presence of Anaplasma marginale and Anaplasma platys-like. These results provide the first molecular evidence for the four above-mentioned tick-borne pathogens in cattle in Bolivia. This information improves our understanding of the epidemiology of TBDs and will help in formulating appropriate and improved pathogen control strategies.

ウエストナイルウイルス感染によるタンパク質の核内輸送への影響　　　　　　　　　　　　　　　
小林 進太郎, 好井 健太朗, 澤 洋文, 苅和 宏明
日本獣医学会学術集会講演要旨集, 164回, [FO, 24], (公社)日本獣医学会, Sep. 2021
Japanese

Attenuated infection by a Pteropine orthoreovirus isolated from an Egyptian fruit bat in Zambia.
Hayato Harima, Michihito Sasaki, Yasuko Orba, Kosuke Okuya, Yongjin Qiu, Christida E Wastika, Katendi Changula, Masahiro Kajihara, Edgar Simulundu, Tomoyuki Yamaguchi, Yoshiki Eto, Akina Mori-Kajihara, Akihiko Sato, Satoshi Taniguchi, Ayato Takada, Masayuki Saijo, Bernard M Hang'ombe, Hirofumi Sawa
PLoS neglected tropical diseases, 15, 9, e0009768, Sep. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, BACKGROUND: Pteropine orthoreovirus (PRV) is an emerging bat-borne zoonotic virus that causes severe respiratory illness in humans. Although PRVs have been identified in fruit bats and humans in Australia and Asia, little is known about the prevalence of PRV infection in Africa. Therefore, this study performed an PRV surveillance in fruit bats in Zambia. METHODS: Egyptian fruit bats (Rousettus aegyptiacus, n = 47) and straw-colored fruit bats (Eidolon helvum, n = 33) captured in Zambia in 2017-2018 were screened for PRV infection using RT-PCR and serum neutralization tests. The complete genome sequence of an isolated PRV strain was determined by next generation sequencing and subjected to BLAST and phylogenetic analyses. Replication capacity and pathogenicity of the strain were investigated using Vero E6 cell cultures and BALB/c mice, respectively. RESULTS: An PRV strain, tentatively named Nachunsulwe-57, was isolated from one Egyptian fruit bat. Serological assays demonstrated that 98% of sera (69/70) collected from Egyptian fruit bats (n = 37) and straw-colored fruit bats (n = 33) had neutralizing antibodies against PRV. Genetic analyses revealed that all 10 genome segments of Nachunsulwe-57 were closely related to a bat-derived Kasama strain found in Uganda. Nachunsulwe-57 showed less efficiency in viral growth and lower pathogenicity in mice than another PRV strain, Miyazaki-Bali/2007, isolated from a patient. CONCLUSIONS: A high proportion of Egyptian fruit bats and straw-colored fruit bats were found to be seropositive to PRV in Zambia. Importantly, a new PRV strain (Nachunsulwe-57) was isolated from an Egyptian fruit bat in Zambia, which had relatively weak pathogenicity in mice. Taken together, our findings provide new epidemiological insights about PRV infection in bats and indicate the first isolation of an PRV strain that may have low pathogenicity to humans.

SARS-CoV-2 Bearing a Mutation at the S1/S2 Cleavage Site Exhibits Attenuated Virulence and Confers Protective Immunity.
Michihito Sasaki, Shinsuke Toba, Yukari Itakura, Herman M Chambaro, Mai Kishimoto, Koshiro Tabata, Kittiya Intaruck, Kentaro Uemura, Takao Sanaki, Akihiko Sato, William W Hall, Yasuko Orba, Hirofumi Sawa
mBio, 12, 4, e0141521, 31 Aug. 2021, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) possesses a discriminative polybasic cleavage motif in its spike protein that is recognized by the host furin protease. Proteolytic cleavage activates the spike protein, thereby affecting both the cellular entry pathway and cell tropism of SARS-CoV-2. Here, we investigated the impact of the furin cleavage site on viral growth and pathogenesis using a hamster animal model infected with SARS-CoV-2 variants bearing mutations at the furin cleavage site (S gene mutants). In the airway tissues of hamsters, the S gene mutants exhibited low growth properties. In contrast to parental pathogenic SARS-CoV-2, hamsters infected with the S gene mutants showed no body weight loss and only a mild inflammatory response, thereby indicating the attenuated variant nature of S gene mutants. This transient infection was sufficient for inducing protective neutralizing antibodies that cross-react with different SARS-CoV-2 lineages. Consequently, hamsters inoculated with S gene mutants showed resistance to subsequent infection with both the parental strain and the currently emerging SARS-CoV-2 variants belonging to lineages B.1.1.7 and P.1. Taken together, our findings revealed that the loss of the furin cleavage site causes attenuation in the airway tissues of hamsters and highlighted the potential benefits of S gene mutants as potential immunogens. IMPORTANCE SARS-CoV-2 uses its spike protein to enter target cells. The spike protein is cleaved by a host protease, and this event facilitates viral entry and broadens cell tropism. In this study, we employed SARS-CoV-2 mutants lacking the S protein cleavage site and characterized their growth and pathogenicity using hamsters, a laboratory animal model for SARS-CoV-2 infection. These mutants exerted low pathogenicity but induced sufficient levels of neutralizing antibodies in hamsters, which protected hamsters from rechallenge with pathogenic clinical SARS-CoV-2 strains. These virus mutants may be used as protective immunogens against SARS-CoV-2 infection.

Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection
Sunanda Baidya, Yoko Nishimoto, Seiichi Sato, Yasuhiro Shimada, Nozomi Sakurai, Hirotaka Nonaka, Koki Noguchi, Mizuki Kido, Satoshi Tadano, Kozo Ishikawa, Kai Li, Aoi Okubo, Taisho Yamada, Yasuko Orba, Michihito Sasaki, Hirofumi Sawa, Hiroko Miyamoto, Ayato Takada, Takashi Nakamura, Akinori Takaoka
Viruses, 13, 9, 1674, 1674, MDPI AG, 24 Aug. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5′-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5′-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.

Mosquito-Borne Viral Pathogens Detected in Zambia: A Systematic Review.
Rachel Milomba Velu, Geoffrey Kwenda, Liyali Libonda, Caroline Cleopatra Chisenga, Bumbangi Nsoni Flavien, Obvious Nchimunya Chilyabanyama, Michelo Simunyandi, Samuel Bosomprah, Nicholus Chintu Sande, Katendi Changula, Walter Muleya, Monicah Mirai Mburu, Benjamin Mubemba, Simbarashe Chitanga, John Tembo, Matthew Bates, Nathan Kapata, Yasuko Orba, Masahiro Kajihara, Ayato Takada, Hirofumi Sawa, Roma Chilengi, Edgar Simulundu
Pathogens (Basel, Switzerland), 10, 8, 10 Aug. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This systematic review aimed to investigate the available evidence of mosquito-borne viral pathogens reported in Zambia. A search of literature was conducted in PubMed and Google Scholar for articles published from 1 January 1930 to 30 June 2020 using a combination of keywords. Eight mosquito-borne viruses belonging to three families, Togaviridae, Flaviviridae and Phenuiviridae were reported. Three viruses (Chikungunya virus, Mayaro virus, Mwinilunga virus) were reported among the togaviruses whilst four (dengue virus, West Nile virus, yellow fever virus, Zika virus) were among the flavivirus and only one virus, Rift Valley fever virus, was reported in the Phenuiviridae family. The majority of these mosquito-borne viruses were reported in Western and North-Western provinces. Aedes and Culex species were the main mosquito-borne viral vectors reported. Farming, fishing, movement of people and rain patterns were among factors associated with mosquito-borne viral infection in Zambia. Better diagnostic methods, such as the use of molecular tools, to detect the viruses in potential vectors, humans, and animals, including the recognition of arboviral risk zones and how the viruses circulate, are important for improved surveillance and design of effective prevention and control measures.

Complete Genome Sequence of a Veterinary Pseudomonas aeruginosa Isolate, Pa12.
Keisuke Nakamura, Jumpei Fujiki, Takaaki Furusawa, Tomohiro Nakamura, Satoshi Gondaira, Michihito Sasaki, Masaru Usui, Hidetoshi Higuchi, Hirofumi Sawa, Yutaka Tamura, Hidetomo Iwano
Microbiology resource announcements, 10, 26, e0039821, Jul. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Pseudomonas aeruginosa causes various opportunistic infections in animals. Here, we report the complete genome sequence of P. aeruginosa strain Pa12, a fluoroquinolone-resistant isolate from a canine skin lesion. To expand the molecular antimicrobial characteristics of the isolate, the whole Pa12 genome was sequenced and assembled via long- and short-read platforms.

RIG-I triggers a signaling-abortive anti-SARS-CoV-2 defense in human lung cells
Taisho Yamada, Seiichi Sato, Yuki Sotoyama, Yasuko Orba, Hirofumi Sawa, Hajime Yamauchi, Michihito Sasaki, Akinori Takaoka
Nature Immunology, 22, 7, 820, 828, Springer Science and Business Media LLC, Jul. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Efficient immune responses against viral infection are determined by sufficient activation of nucleic acid sensor-mediated innate immunity1,2. Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global pandemic. It is an urgent challenge to clarify the innate recognition mechanism to control this virus. Here we show that retinoic acid-inducible gene-I (RIG-I) sufficiently restrains SARS-CoV-2 replication in human lung cells in a type I/III interferon (IFN)-independent manner. RIG-I recognizes the 3' untranslated region of the SARS-CoV-2 RNA genome via the helicase domains, but not the C-terminal domain. This new mode of RIG-I recognition does not stimulate its ATPase, thereby aborting the activation of the conventional mitochondrial antiviral-signaling protein-dependent pathways, which is in accordance with lack of cytokine induction. Nevertheless, the interaction of RIG-I with the viral genome directly abrogates viral RNA-dependent RNA polymerase mediation of the first step of replication. Consistently, genetic ablation of RIG-I allows lung cells to produce viral particles that expressed the viral spike protein. By contrast, the anti-SARS-CoV-2 activity was restored by all-trans retinoic acid treatment through upregulation of RIG-I protein expression in primary lung cells derived from patients with chronic obstructive pulmonary disease. Thus, our findings demonstrate the distinctive role of RIG-I as a restraining factor in the early phase of SARS-CoV-2 infection in human lung cells.

Screening of tick-borne pathogens in argasid ticks in Zambia: Expansion of the geographic distribution of Rickettsia lusitaniae and Rickettsia hoogstraalii and detection of putative novel Anaplasma species.
Yongjin Qiu, Martin Simuunza, Masahiro Kajihara, Herman Chambaro, Hayato Harima, Yoshiki Eto, Edgar Simulundu, David Squarre, Shiho Torii, Ayato Takada, Bernard Mudenda Hang'ombe, Hirofumi Sawa, Chihiro Sugimoto, Ryo Nakao
Ticks and tick-borne diseases, 12, 4, 101720, 101720, Jul. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Ticks (Ixodidae and Argasidae) are important arthropod vectors of various pathogens that cause human and animal infectious diseases. Many previously published studies on tick-borne pathogens focused on those transmitted by ixodid ticks. Although there are increasing reports of viral pathogens associated with argasid ticks, information on bacterial pathogens they transmit is scarce. The aim of this molecular study was to detect and characterize Rickettsia and Anaplasmataceae in three different argasid tick species, Ornithodoros faini, Ornithodoros moubata, and Argas walkerae collected in Zambia. Rickettsia hoogstraalii and Rickettsia lusitaniae were detected in 77 % (77/100) of Ar. walkerae and 10 % (5/50) of O. faini, respectively. All O. moubata pool samples (n = 124) were negative for rickettsial infections. Anaplasmataceae were detected in 63 % (63/100) of Ar. walkerae and in 82.2 % (102/124) of O. moubata pools, but not in O. faini. Phylogenetic analysis based on the concatenated sequences of 16S rRNA and groEL genes revealed that Anaplasma spp. detected in the present study were distinct from previously validated Anaplasma species, indicating that the current knowledge on the diversity and vector range of Anaplasma spp. is incomplete. Our findings highlight new geographical records of R. lusitaniae and R. hoogstraalii and confirm that the wide geographic distribution of these species includes the African continent. The data presented here increase our knowledge on argasid tick-borne bacteria and contribute toward understanding their epidemiology.

Serological Evidence of Filovirus Infection in Nonhuman Primates in Zambia.
Katendi Changula, Edgar Simulundu, Boniface Pongombo Lombe, Eri Nakayama, Hiroko Miyamoto, Yuji Takahashi, Hirofumi Sawa, Chuma Simukonda, Bernard M Hang'ombe, Ayato Takada
Viruses, 13, 7, 30 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Ebolaviruses and marburgviruses are filoviruses that are known to cause severe hemorrhagic fever in humans and nonhuman primates (NHPs). While some bat species are suspected to be natural reservoirs of these filoviruses, wild NHPs often act as intermediate hosts for viral transmission to humans. Using an enzyme-linked immunosorbent assay, we screened two NHP species, wild baboons and vervet monkeys captured in Zambia, for their serum IgG antibodies specific to the envelope glycoproteins of filoviruses. From 243 samples tested, 39 NHPs (16%) were found to be seropositive either for ebolaviruses or marburgviruses with endpoint antibody titers ranging from 100 to 25,600. Interestingly, antibodies reactive to Reston virus, which is found only in Asia, were detected in both NHP species. There was a significant difference in the seropositivity for the marburgvirus antigen between the two NHP species, with baboons having a higher positive rate. These results suggest that wild NHPs in Zambia might be nonlethally exposed to these filoviruses, and this emphasizes the need for continuous monitoring of filovirus infection in wild animals to better understand the ecology of filoviruses and to assess potential risks of outbreaks in humans in previously nonendemic countries.

Safety enhancement of a genetically modified live rabies vaccine strain by introducing an attenuating Leu residue at position 333 in the glycoprotein.
Naoto Ito, Takuya Okamoto, Michihito Sasaki, Shoya Miyamoto, Tatsuki Takahashi, Fumiki Izumi, Maho Inukai, Supasiri Jarusombuti, Kazuma Okada, Kento Nakagawa, Yuji Fujii, Shoko Nishiyama, Tatsunori Masatani, Hirofumi Sawa, Makoto Sugiyama
Vaccine, 39, 28, 3777, 3784, 23 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, To improve the safety of genetically modified live rabies vaccine strains, most studies have utilized an attenuating Arg-to-Glu mutation at position 333 in the glycoprotein (G333), which is responsible for attenuation of the live vaccine strain SAG2. The Glu residue requires two nucleotide substitutions to revert to pathogenic Arg, thus significantly lowering the probability of pathogenic reversion caused by the Glu-to-Arg mutation at G333. However, only one nucleotide substitution is sufficient to convert the Glu residue to another pathogenic residue, Lys, and thereby to cause pathogenic reversion. This indicates a potential safety problem of SAG2 and the live vaccine candidates attenuated by Glu at G333. In this study, aiming to solve this problem, we examined the utility of a Leu residue, which requires two nucleotide substitutions to be both Arg and Lys, as an attenuating mutation at G333. Using a reverse genetics system of the live vaccine strain ERA, we generated ERA-G333Leu by introducing an Arg-to-Leu mutation at G333. Similar to ERA-G333Glu, which is attenuated by an Arg-to-Glu mutation at G333, ERA-G333Leu did not cause obvious clinical signs in 6-week-old mice after intracerebral inoculation. Importantly, after 10 passages in suckling mouse brains, ERA-G333Glu acquired a pathogenic Lys or Arg at G333 and a high level of lethality in mice, whereas ERA-G333Leu retained the attenuating Leu at G333 and only showed a modest level of virulence probably caused by a mutation at G194. In addition, ERA-G333Leu and ERA-G333Glu induced neutralizing antibody response and protective immunity in mice with similar efficiencies. The results demonstrate that, compared to ERA-G333Glu, ERA-G333Leu is more stably attenuated, also indicating the high utility of a Leu residue as an attenuating mutation at G333 in the development of live rabies vaccine strains with a high level of safety.

Molecular Detection and Genotyping of Coxiella-Like Endosymbionts in Ticks Collected from Animals and Vegetation in Zambia.
Toshiya Kobayashi, Elisha Chatanga, Yongjin Qiu, Martin Simuunza, Masahiro Kajihara, Bernard Mudenda Hang'ombe, Yoshiki Eto, Ngonda Saasa, Akina Mori-Kajihara, Edgar Simulundu, Ayato Takada, Hirofumi Sawa, Ken Katakura, Nariaki Nonaka, Ryo Nakao
Pathogens (Basel, Switzerland), 10, 6, 21 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Ticks are obligate ectoparasites as they require to feed on their host blood during some or all stages of their life cycle. In addition to the pathogens that ticks harbor and transmit to vertebrate hosts, they also harbor other seemingly nonpathogenic microorganisms including nutritional mutualistic symbionts. Tick nutritional mutualistic symbionts play important roles in the physiology of the host ticks as they are involved in tick reproduction and growth through the supply of B vitamins as well as in pathogen maintenance and propagation. Coxiella-like endosymbionts (CLEs) are the most widespread endosymbionts exclusively reported in ticks. Although CLEs have been investigated in ticks in other parts of the world, there is no report of their investigation in ticks in Zambia. To investigate the occurrence of CLEs, their maintenance, and association with host ticks in Zambia, 175 ticks belonging to six genera, namely Amblyomma, Argas, Haemaphysalis, Hyalomma, Ornithodoros, and Rhipicephalus, were screened for CLEs, followed by characterization of CLEs by multi-locus sequence typing of the five Coxiella housekeeping genes (dnaK, groEL, rpoB, 16S rRNA, and 23S rRNA). The results showed that 45.7% (n = 80) were positive for CLEs. The comparison of the tick 16S rDNA phylogenetic tree with that of the CLEs concatenated sequences showed that there was a strong correlation between the topology of the trees. The results suggest that most of the CLEs have evolved within tick species, supporting the vertical transmission phenomenon. However, the negative results for CLE in some ticks warrants further investigations of other endosymbionts that the ticks in Zambia may also harbor.

Immunization Coverage and Antibody Retention against Rabies in Domestic Dogs in Lusaka District, Zambia
Chiho Kaneko, Michihito Sasaki, Ryosuke Omori, Ryo Nakao, Chikako Kataoka-Nakamura, Ladslav Moonga, Joseph Ndebe, Walter Muleya, Edgar Simulundu, Bernard M. Hang’ombe, George Dautu, Masahiro Kajihara, Akina Mori-Kajihara, Yongjin Qiu, Naoto Ito, Herman M. Chambaro, Chihiro Sugimoto, Hideaki Higashi, Ayato Takada, Hirofumi Sawa, Aaron S. Mweene, Norikazu Isoda
Pathogens, 10, 6, 738, 738, MDPI AG, 11 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Rabies remains endemic in Zambia. Despite conducting canine vaccinations in Lusaka district, the vaccination coverage and actual seropositivity in the dog population in Lusaka district are rarely evaluated. This study estimated the seropositivity-based immunization coverage in the owned dog population in Lusaka district using the expanded program on immunization cluster survey method. The time-series trend of neutralizing antibodies against rabies in vaccinated dogs was also evaluated. Of 366 dogs in 200 dog-owning households in Lusaka district, blood samples were collected successfully from 251 dogs. In the sampled dogs, 42.2% (106/251) had an antibody titer ≥0.5 IU/mL. When the 115 dogs whose blood was not collected were assumed to be seronegative, the minimum immunization coverage in Lusaka district’s owned dog population was estimated at 29.0% (95% confidence interval: 22.4–35.5). It was also found that a single vaccination with certified vaccines is capable of inducing protective levels of antibodies. In contrast, higher antibody titers were observed in multiple-vaccinated dogs than in single-vaccinated dogs, coupled with the observation of a decline in antibody titer over time. These results suggest the importance of continuous booster immunization to maintain herd immunity and provide useful information to plan mass vaccination against rabies in Zambia.

Serologic and molecular evidence for circulation of Crimean-Congo hemorrhagic fever virus in ticks and cattle in Zambia.
Masahiro Kajihara, Martin Simuunza, Ngonda Saasa, George Dautu, Akina Mori-Kajihara, Yongjin Qiu, Ryo Nakao, Yoshiki Eto, Hayato Furumoto, Bernard M Hang'ombe, Yasuko Orba, Hirofumi Sawa, Edgar Simulundu, Shuetsu Fukushi, Shigeru Morikawa, Masayuki Saijo, Jiro Arikawa, Swithine Kabilika, Mwaka Monze, Victor Mukonka, Aaron Mweene, Ayato Takada, Kumiko Yoshimatsu
PLoS neglected tropical diseases, 15, 6, e0009452, Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonosis with a high case fatality rate in humans. Although the disease is widely found in Africa, Europe, and Asia, the distribution and genetic diversity of CCHF virus (CCHFV) are poorly understood in African countries. To assess the risks of CCHF in Zambia, where CCHF has never been reported, epidemiologic studies in cattle and ticks were conducted. Through an indirect immunofluorescence assay, CCHFV nucleoprotein-specific serum IgG was detected in 8.4% (88/1,047) of cattle. Among 290 Hyalomma ticks, the principal vector of CCHFV, the viral genome was detected in 11 ticks. Phylogenetic analyses of the CCHFV S and M genome segments revealed that one of the detected viruses was a genetic reassortant between African and Asian strains. This study provides compelling evidence for the presence of CCHFV in Zambia and its transmission to vertebrate hosts.

First Molecular Detection of Coxiella burnetii in Beef Cattle in West Java, Indonesia.
Elok Puspita Rini, Michihito Sasaki, Dwi Astuti, Vetnizah Juniantito, I Wayan Teguh Wibawan, Hirofumi Sawa, Agus Setiyono
Japanese journal of infectious diseases, 75, 1, 83, 85, 30 Apr. 2021, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Coxiella burnetii (C. burnetii) is a bacterial agent causing Q fever which is widespread all over the world. Livestock such as cattle, goat, and sheep are the main sources of infection for this disease. Infection of C. burnetii causes abortion of livestock, resulting in economic damage. Q fever is zoonotic disease and potential public health hazard. To date, little is known about the infection of C. burnetii in livestock in Indonesia. The objective of this research is to screen the genome of C. burnetii bacteria in beef cattle in West Java, Indonesia. Organ tissue samples were collected from cattle slaughtered in slaughterhouses, West Java. C. burnetii genome was detected from cattle samples in all three samplings area by nested PCR (nPCR) targeting com1 gene of C. burnetii. Sequencing analysis of 16S rRNA gene revealed the amplicons showed 99.9% nucleotide identity to C. burnetii strains Heizberg, 1843, 2574, 701CbB1, and 14160-001. Our results indicate that the infection of C. burnetii occurs in Indonesian beef cattles and highlight the risk of exposure to C. burnetii infection in human.

Domestic dog demographics and estimates of canine vaccination coverage in a rural area of Zambia for the elimination of rabies
Chiho Kaneko, Ryosuke Omori, Michihito Sasaki, Chikako Kataoka-Nakamura, Edgar Simulundu, Walter Muleya, Ladslav Moonga, Joseph Ndebe, Bernard M. Hang’ombe, George Dautu, Yongjin Qiu, Ryo Nakao, Masahiro Kajihara, Akina Mori-Kajihara, Herman M. Chambaro, Hideaki Higashi, Chihiro Sugimoto, Hirofumi Sawa, Aaron S. Mweene, Ayato Takada, Norikazu Isoda
PLOS Neglected Tropical Diseases, 15, 4, e0009222, e0009222, Public Library of Science (PLoS), 28 Apr. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal,

An estimated 75% or more of the human rabies cases in Africa occur in rural settings, which underscores the importance of rabies control in these areas. Understanding dog demographics can help design strategies for rabies control and plan and conduct canine mass vaccination campaigns effectively in African countries.





A cross-sectional survey was conducted to investigate domestic dog demographics in Kalambabakali, in the rural Mazabuka District of Zambia. The population of ownerless dogs and the total achievable vaccination coverage among the total dog population was estimated using the capture-recapture-based Bayesian model by conducting a canine mass vaccination campaign. This study revealed that 29% of the domestic dog population was under one year old, and 57.7% of those were under three months old and thus were not eligible for the canine rabies vaccination in Zambia. The population growth was estimated at 15% per annum based on the cross-sectional household survey. The population of ownerless dogs was estimated to be small, with an ownerless-to-owned-dog ratio of 0.01–0.06 in the target zones. The achieved overall vaccination coverage from the first mass vaccination was estimated 19.8–51.6%. This low coverage was principally attributed to the owners’ lack of information, unavailability, and dog-handling difficulties. The follow-up mass vaccination campaign achieved an overall coverage of 54.8–76.2%.





This paper indicates the potential for controlling canine rabies through mass vaccination in rural Zambia. Rabies education and responsible dog ownership are required to achieve high and sustainable vaccination coverage. Our findings also propose including puppies below three months old in the target population for rabies vaccination and emphasize that securing an annual enforcement of canine mass vaccination that reaches 70% coverage in the dog population is necessary to maintain protective herd immunity.

First report of Mycobacterium bovis in wild chacma baboons (Papio ursinus) at the human-wildlife interface area in Zambia.
David Squarre, Joseph Chizimu, Chie Nakajima, John B Muma, Bernard M Hang'ombe, Edgar Simulundu, Wizaso Mwasinga, Jackson Katampi, Paul Fandamu, Victor Mukonka, Yasuhiko Suzuki, Hirofumi Sawa, Hetron M Munang'andu, Griffin Shanungu, Herman M Chambaro, Musso Munyeme
Transboundary and emerging diseases, 69, 3, 1659, 1662, 26 Apr. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Mycobacterium bovis (M. bovis) causes tuberculosis in mammals and is a major public health threat worldwide. While M. bovis has been reported in humans, domestic and wild ruminants at the human-wildlife-livestock interface area in Zambia, there is paucity of information on the role of primates as reservoir hosts. We screened seven wild chacma baboons (Papio ursinus) for tuberculosis at the human-wildlife interface area in Lochinvar National Park in the Kafue Flats, Zambia. Following necropsy, lung tissue and associated lymph nodes with tuberculous-like lesions collected from four adult male baboons were prepared for Mycobacterium culture. The isolates were initially typed using the Mycobacterium tuberculosis complex-discrimination multiplex PCR assay and further characterized by spoligotyping and 26-loci MIRU-VNTR. Mycobacteria were isolated from all four animals and identified as M. bovis by PCR. On Spoligotyping, all isolates belonged to SB 0120 spoligotype, which is similar to what was previously reported in humans, cattle and Kafue lechwe antelopes in Kafue Flats ecosystem. Furthermore, on MIRU-VNTR typing, the baboon isolates clustered with cattle and Kafue lechwe isolates from the same catchment area. This finding intimates probable cross-species transmission of M. bovis in the Kafue Flats ecosystem. Due to the close interaction of baboons and humans at interface areas in Zambia, our results have potential implications for public health. Equally, this finding raises concerns for conservation.

Combinatorial approach with mass spectrometry and lectin microarray dissected glycoproteomic features of virion-derived spike protein of SARS-CoV-2
Takahiro Hiono, Azusa Tomioka, Hiroyuki Kaji, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Atsushi Kuno
Cold Spring Harbor Laboratory, 12 Apr. 2021, [Peer-reviewed]
The COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, has a global impact on public health. Since glycosylation of the viral envelope glycoproteins is known to be deeply associated with their immunogenicity, intensive studies on the glycans of its major glycoprotein, S protein, have been conducted. Nevertheless, the detailed site-specific glycan compositions of virion-associated S protein have not yet been clarified. Here, we conducted intensive glycoproteomic analyses of SARS-CoV-2 S protein using a combinatorial approach with two different technologies: mass spectrometry (MS) and lectin microarray. Using our unique MS1-based glycoproteomic technique, Glyco-RIDGE, in addition to MS2-based Byonic search, we identified 1,759 site-specific glycan compositions. The most frequent was HexNAc:Hex:Fuc:NeuAc:NeuGc = 6:6:1:0:0, suggesting a tri-antennary N-glycan terminating with LacNAc and having bisecting GlcNAc and a core fucose, which was found in 20 of 22 glycosylated sites. The subsequent lectin microarray analysis emphasized intensive outer arm fucosylation of glycans, which efficiently complemented the glycoproteomic features. The present results illustrate the high-resolution glycoproteomic features of SARS-CoV-2 S protein and significantly contribute to vaccine design, as well as the understanding of viral protein synthesis.

Host serine proteases TMPRSS2 and TMPRSS11D mediate proteolytic activation and trypsin-independent infection in group A rotaviruses.
Michihito Sasaki, Yukari Itakura, Mai Kishimoto, Koshiro Tabata, Kentaro Uemura, Naoto Ito, Makoto Sugiyama, Christida E Wastika, Yasuko Orba, Hirofumi Sawa
Journal of virology, 95, 11, 24 Mar. 2021, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Group A rotaviruses (RVAs) are representative enteric virus species and major causes of diarrhea in humans and animals. The RVA virion is a triple-layered particle, and the outermost layer consists of the glycoprotein VP7 and spike protein VP4. To increase the infectivity of RVA, VP4 is proteolytically cleaved into VP5* and VP8* subunits by trypsin; and these subunits form a rigid spike structure on the virion surface. In this study, we investigated the growth of RVAs in cells transduced with type II transmembrane serine proteases (TTSPs), which cleave fusion proteins and promote infection by respiratory viruses, such as influenza viruses, paramyxoviruses, and coronaviruses. We identified TMPRSS2 and TMPRSS11D as host TTSPs that mediate trypsin-independent and multi-cycle infection by human and animal RVA strains. In vitro cleavage assays revealed that recombinant TMPRSS11D cleaved RVA VP4. We also found that TMPRSS2 and TMPRSS11D promote the infectious entry of immature RVA virions, but they could not activate nascent progeny virions in the late phase of infection. This observation differed from the TTSP-mediated activation process of paramyxoviruses, revealing the existence of virus species-specific activation processes in TTSPs. Our study provides new insights into the interaction between RVAs and host factors, and TTSP-transduced cells offer potential advantages for RVA research and development.ImportanceProteolytic cleavage of the viral VP4 protein is essential for virion maturation and infectivity in group A rotaviruses (RVAs). In cell culture, RVAs are propagated in culture medium supplemented with the exogenous protease trypsin, which cleaves VP4 and induces the maturation of progeny RVA virions. In this study, we demonstrated that the host proteases TMPRSS2 and TMPRSS11D mediate the trypsin-independent infection and growth of RVA. Our data revealed that the proteolytic activation of RVAs by TMPRSS2 and TMPRSS11D occurs at the viral entry step. Because TMPRSS2 and TMPRSS11D gene expression induced similar or higher levels of RVA growth as trypsin-supplemented culture, this approach offers potential advantages for RVA research and development.

MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2.
Kentaro Uemura, Michihito Sasaki, Takao Sanaki, Shinsuke Toba, Yoshimasa Takahashi, Yasuko Orba, William W Hall, Katsumi Maenaka, Hirofumi Sawa, Akihiko Sato
Scientific reports, 11, 1, 5376, 5376, 08 Mar. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Although the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a worldwide pandemic, there are currently no virus-specific drugs that are fully effective against SARS-CoV-2. Only a limited number of human-derived cells are capable of supporting SARS-CoV-2 replication and the infectivity of SARS-CoV-2 in these cells remains poor. In contrast, monkey-derived Vero cells are highly susceptibility to infection with SARS-CoV-2, although they are not suitable for the study of antiviral effects by small molecules due to their limited capacity to metabolize drugs compared to human-derived cells. In this study, our goal was to generate a virus-susceptible human cell line that would be useful for the identification and testing of candidate drugs. Towards this end, we stably transfected human lung-derived MRC5 cells with a lentiviral vector encoding angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2. Our results revealed that SARS-CoV-2 replicates efficiently in MRC5/ACE2 cells. Furthermore, viral RNA replication and progeny virus production were significantly reduced in response to administration of the replication inhibitor, remdesivir, in MRC5/ACE2 cells compared with Vero cells. We conclude that the MRC5/ACE2 cells will be important in developing specific anti-viral therapeutics and will assist in vaccine development to combat SARS-CoV-2 infections.

Prevalence and genetic diversity of Shibuyunji virus, a novel tick-borne phlebovirus identified in Zambia.
Edgar Simulundu, Saidon Mbambara, Herman M Chambaro, Karen Sichibalo, Masahiro Kajihara, King S Nalubamba, Hirofumi Sawa, Ayato Takada, Katendi Changula, Simbarashe Chitanga
Archives of virology, 166, 3, 915, 919, Mar. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Tick-borne pathogens are an emerging public health threat worldwide. However, information on tick-borne viruses is scanty in sub-Saharan Africa. Here, by RT-PCR, 363 ticks (Amblyomma, Hyalomma and Rhipicephalus) in the Namwala and Livingstone districts of Zambia were screened for tick-borne phleboviruses (TBPVs). TBPVs (L gene) were detected in 19 (5.2%) Rhipicephalus ticks in Namwala. All the detected TBPVs were Shibuyunji viruses. Phylogenetically, they were closely related to American dog tick phlebovirus. This study highlights the possible role of Rhipicephalus ticks as the main host of Shibuyunji virus and suggests that these viruses may be present outside the area where they were initially discovered.

Mastomys natalensis is a possible natural rodent reservoir for encephalomyocarditis virus.
Mai Kishimoto, Bernard M Hang'ombe, William W Hall, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
The Journal of general virology, 102, 3, Mar. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Encephalomyocarditis virus (EMCV) infects a wide range of hosts and can cause encephalitis, myocarditis, reproductive disorders and diabetes mellitus in selected mammalian species. As for humans, EMCV infection seems to occur by the contact with animals and can cause febrile illnesses in some infected patients. Here we isolated EMCV strain ZM12/14 from a natal multimammate mouse (Mastomys natalensis: M. natalensis) in Zambia. Pairwise sequence similarity of the ZM12/14 P1 region consisting of antigenic capsid proteins showed the highest similarity of nucleotide (80.7 %) and amino acid (96.2%) sequence with EMCV serotype 1 (EMCV-1). Phylogenetic analysis revealed that ZM12/14 clustered into EMCV-1 at the P1 and P3 regions but segregated from known EMCV strains at the P2 region, suggesting a unique evolutionary history. Reverse transcription PCR (RT-PCR) screening and neutralizing antibody assays for EMCV were performed using collected tissues and serum from various rodents (n=179) captured in different areas in Zambia. We detected the EMCV genome in 19 M. natalensis (19/179=10.6 %) and neutralizing antibody for EMCV in 33 M. natalensis (33/179=18.4 %). However, we did not detect either the genome or neutralizing antibody in other rodent species. High neutralizing antibody litres (≧320) were observed in both RT-PCR-negative and -positive animals. Inoculation of ZM12/14 caused asymptomatic persistent infection in BALB/c mice with high antibody titres and high viral loads in some organs, consistent with the above epidemiological results. This study is the first report of the isolation of EMCV in Zambia, suggesting that M. natalensis may play a role as a natural reservoir of infection.

Diverse mosquito-specific flaviviruses in the Bolivian Amazon basin.
Yasuko Orba, Keita Matsuno, Ryo Nakao, Kirill Kryukov, Yumi Saito, Fumihiko Kawamori, Ariel Loza Vega, Tokiko Watanabe, Tadashi Maemura, Michihito Sasaki, William W Hall, Roy A Hall, Juan Antonio Pereira, So Nakagawa, Hirofumi Sawa
The Journal of general virology, 102, 3, Mar. 2021, [Last author], [International Magazine]
English, Scientific journal, The genus Flavivirus includes a range of mosquito-specific viruses in addition to well-known medically important arboviruses. Isolation and comprehensive genomic analyses of viruses in mosquitoes collected in Bolivia resulted in the identification of three novel flavivirus species. Psorophora flavivirus (PSFV) was isolated from Psorophora albigenu. The coding sequence of the PSFV polyprotein shares 60 % identity with that of the Aedes-associated lineage II insect-specific flavivirus (ISF), Marisma virus. Isolated PSFV replicates in both Aedes albopictus- and Aedes aegypti-derived cells, but not in mammalian Vero or BHK-21 cell lines. Two other flaviviruses, Ochlerotatus scapularis flavivirus (OSFV) and Mansonia flavivirus (MAFV), which were identified from Ochlerotatus scapularis and Mansonia titillans, respectively, group with the classical lineage I ISFs. The protein coding sequences of these viruses share only 60 and 40 % identity with the most closely related of known lineage I ISFs, including Xishuangbanna aedes flavivirus and Sabethes flavivirus, respectively. Phylogenetic analysis suggests that MAFV is clearly distinct from the groups of the current known Culicinae-associated lineage I ISFs. Interestingly, the predicted amino acid sequence of the MAFV capsid protein is approximately two times longer than that of any of the other known flaviviruses. Our results indicate that flaviviruses with distinct features can be found at the edge of the Bolivian Amazon basin at sites that are also home to dense populations of human-biting mosquitoes.

An African tick flavivirus forming an independent clade exhibits unique exoribonuclease-resistant RNA structures in the genomic 3'-untranslated region.
Hayato Harima, Yasuko Orba, Shiho Torii, Yongjin Qiu, Masahiro Kajihara, Yoshiki Eto, Naoya Matsuta, Bernard M Hang'ombe, Yuki Eshita, Kentaro Uemura, Keita Matsuno, Michihito Sasaki, Kentaro Yoshii, Ryo Nakao, William W Hall, Ayato Takada, Takashi Abe, Michael T Wolfinger, Martin Simuunza, Hirofumi Sawa
Scientific reports, 11, 1, 4883, 4883, 01 Mar. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Tick-borne flaviviruses (TBFVs) infect mammalian hosts through tick bites and can cause various serious illnesses, such as encephalitis and hemorrhagic fevers, both in humans and animals. Despite their importance to public health, there is limited epidemiological information on TBFV infection in Africa. Herein, we report that a novel flavivirus, Mpulungu flavivirus (MPFV), was discovered in a Rhipicephalus muhsamae tick in Zambia. MPFV was found to be genetically related to Ngoye virus detected in ticks in Senegal, and these viruses formed a unique lineage in the genus Flavivirus. Analyses of dinucleotide contents of flaviviruses indicated that MPFV was similar to those of other TBFVs with a typical vertebrate genome signature, suggesting that MPFV may infect vertebrate hosts. Bioinformatic analyses of the secondary structures in the 3'-untranslated regions (UTRs) revealed that MPFV exhibited unique exoribonuclease-resistant RNA (xrRNA) structures. Utilizing biochemical approaches, we clarified that two xrRNA structures of MPFV in the 3'-UTR could prevent exoribonuclease activity. In summary, our findings provide new information regarding the geographical distribution of TBFV and xrRNA structures in the 3'-UTR of flaviviruses.

TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein.
Mai Kishimoto, Kentaro Uemura, Takao Sanaki, Akihiko Sato, William W Hall, Hiroaki Kariwa, Yasuko Orba, Hirofumi Sawa, Michihito Sasaki
Viruses, 13, 3, 28 Feb. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.

Detection of B.1.351 SARS-CoV-2 Variant Strain - Zambia, December 2020.
Mulenga Mwenda, Ngonda Saasa, Nyambe Sinyange, George Busby, Peter J Chipimo, Jason Hendry, Otridah Kapona, Samuel Yingst, Jonas Z Hines, Peter Minchella, Edgar Simulundu, Katendi Changula, King Shimumbo Nalubamba, Hirofumi Sawa, Masahiro Kajihara, Junya Yamagishi, Muzala Kapin'a, Nathan Kapata, Sombo Fwoloshi, Paul Zulu, Lloyd B Mulenga, Simon Agolory, Victor Mukonka, Daniel J Bridges
MMWR. Morbidity and mortality weekly report, 70, 8, 280, 282, 26 Feb. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, The first laboratory-confirmed cases of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV-2, in Zambia were detected in March 2020 (1). Beginning in July, the number of confirmed cases began to increase rapidly, first peaking during July-August, and then declining in September and October (Figure). After 3 months of relatively low case counts, COVID-19 cases began rapidly rising throughout the country in mid-December. On December 18, 2020, South Africa published the genome of a SARS-CoV-2 variant strain with several mutations that affect the spike protein (2). The variant included a mutation (N501Y) associated with increased transmissibility.†,§ SARS-CoV-2 lineages with this mutation have rapidly expanded geographically.¶,** The variant strain (PANGO [Phylogenetic Assignment of Named Global Outbreak] lineage B.1.351††) was first detected in the Eastern Cape Province of South Africa from specimens collected in early August, spread within South Africa, and appears to have displaced the majority of other SARS-CoV-2 lineages circulating in that country (2). As of January 10, 2021, eight countries had reported cases with the B.1.351 variant. In Zambia, the average number of daily confirmed COVID-19 cases increased 16-fold, from 44 cases during December 1-10 to 700 during January 1-10, after detection of the B.1.351 variant in specimens collected during December 16-23. Zambia is a southern African country that shares substantial commerce and tourism linkages with South Africa, which might have contributed to the transmission of the B.1.351 variant between the two countries.

Inactivation of sars-cov-2 by povidone-iodine products: Implications for effective mouth rinsing and gargling
Hiroaki Kariwa, Hirofumi Sawa, Shintaro Kobayashi
Japanese Journal of Veterinary Research, 69, 3, 183, 187, Hokkaido University, 2021
English, Scientific journal

First COVID-19 case in Zambia - Comparative phylogenomic analyses of SARS-CoV-2 detected in African countries.
Edgar Simulundu, Francis Mupeta, Pascalina Chanda-Kapata, Ngonda Saasa, Katendi Changula, Walter Muleya, Simbarashe Chitanga, Miniva Mwanza, Paul Simusika, Herman Chambaro, Benjamin Mubemba, Masahiro Kajihara, Duncan Chanda, Lloyd Mulenga, Sombo Fwoloshi, Aaron Lunda Shibemba, Fred Kapaya, Paul Zulu, Kunda Musonda, Mwaka Monze, Nyambe Sinyange, Mazyanga L Mazaba, Muzala Kapin'a, Peter J Chipimo, Raymond Hamoonga, Davie Simwaba, William Ngosa, Albertina N Morales, Nkomba Kayeyi, John Tembo, Mathew Bates, Yasuko Orba, Hirofumi Sawa, Ayato Takada, King S Nalubamba, Kennedy Malama, Victor Mukonka, Alimuddin Zumla, Nathan Kapata
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 102, 455, 459, Jan. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. While African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 h of the individual entering the country by air travel from a trip to France. Contact tracing showed that SARS-CoV-2 infection was contained within the patient's household, with no further spread to attending health care workers or community members. Phylogenomic analysis of the patient's SARS-CoV-2 strain showed that it belonged to lineage B.1.1., sharing the last common ancestor with SARS-CoV-2 strains recovered from South Africa. At the African continental level, our analysis showed that B.1 and B.1.1 lineages appear to be predominant in Africa. Whole genome sequence analysis should be part of all surveillance and case detection activities in order to monitor the origin and evolution of SARS-CoV-2 lineages across Africa.

SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells.
Michihito Sasaki, Kentaro Uemura, Akihiko Sato, Shinsuke Toba, Takao Sanaki, Katsumi Maenaka, William W Hall, Yasuko Orba, Hirofumi Sawa
PLoS pathogens, 17, 1, e1009233, Jan. 2021, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains.

The occurrence of coxiella burnetiid nfection in local goat in malang, East Java, Indonesia: A first report　　　　　　　　　　　　　　　
Handayu Untari, Agus Setiyono, Ekowati Handharyani, Masdiana C. Padaga, Dwi Astuti, Michihito Sasaki, Hirofumi Sawa
Veterinary Practitioner, 21, 2, 488, 493, Veterinary Practitioner, 01 Dec. 2020
English, Scientific journal

Identification of quinolone derivatives as effective anti-Dengue virus agents.
Haruaki Nobori, Kentaro Uemura, Shinsuke Toba, Takao Sanaki, Takao Shishido, William W Hall, Yasuko Orba, Hirofumi Sawa, Akihiko Sato
Antiviral research, 184, 104969, 104969, Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Dengue virus (DENV) infection is one of the most important infectious diseases in tropical and subtropical regions around the world. Previously, we performed an initial phenotypic screening of 7000 compounds using DENV type 2 (DENV2)-infected BHK-21 cells to identify small molecules which could inhibit virus replication. In this study, we describe two novel compounds with anti-DENV2 activity, tentatively named Compound-X and Compound-Y. Both compounds possess a quinolone skeleton, and the EC50s of Compound-X and Compound-Y against DENV2 were 3.9 μM and 9.2 μM, respectively. Based on a DENV replicon assay, it was suggested that these compounds have anti-DENV2 activity by inhibition of a step in virus replication. Furthermore, using mutational analysis we obtained compounds-resistant to DENV2 infection and identified a mutation, V130A in the NS5 methyltransferase (MTase) domain. However, these compounds did not inhibit MTase activity. In addition, incorporation of an additional NS1 N246D mutation with the NS5 V130A mutation in DENV2 resulted in recovery of viral replication and a further reduction of the sensitivity to the quinolone compounds by an unknown mechanism. Therefore further investigations are required to clarify the antiviral mechanisms of these quinolone compounds.

Whole-Genome Sequence of Fluoroquinolone-Resistant Escherichia coli HUE1, Isolated in Hokkaido, Japan.
Montgomery Munby, Jumpei Fujiki, Kotaro Aoki, Chika Kawaguchi, Keisuke Nakamura, Tomohiro Nakamura, Michihito Sasaki, Toyotaka Sato, Masaru Usui, Hirofumi Sawa, Shin-Ichi Yokota, Yutaka Tamura, Hidetomo Iwano
Microbiology resource announcements, 9, 46, 12 Nov. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, We report the complete genome sequence of Escherichia coli strain HUE1, isolated from the urinary catheter of a female patient, showing fluoroquinolone resistance without quinolone resistance-determining region mutations. To facilitate the exploration of the molecular characteristics of HUE1, the whole genome was sequenced using long- and short-read platforms.

Susceptibility of Pseudomonas aeruginosa veterinary isolates to Pbunavirus PB1-like phages.
Jumpei Fujiki, Takaaki Furusawa, Montgomery Munby, Chika Kawaguchi, Yumie Matsuda, Yusei Shiokura, Keisuke Nakamura, Tomohiro Nakamura, Michihito Sasaki, Masaru Usui, Tomohito Iwasaki, Satoshi Gondaira, Hidetoshi Higuchi, Hirofumi Sawa, Yutaka Tamura, Hidetomo Iwano
Microbiology and immunology, 64, 11, 778, 782, Nov. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, In recent years, antimicrobial-resistant Pseudomonas aeruginosa strains have increased in the veterinary field. Therefore, phage therapy has received significant attention as an approach for overcoming antimicrobial resistance. In this context, we isolated and characterized four Pseudomonas bacteriophages. Phylogenetic analysis showed that the isolated phages are novel Myoviridae Pbunavirus PB1-like phages with ØR12 belonging to a different clade compared with the other three. These phages had distinct lytic activity against 22 P. aeruginosa veterinary isolates. The phage cocktail composed from the PB1-like phages clearly inhibited the occurrence of the phage-resistant variant, suggesting that these phages could be useful in phage therapy.

The Lethal(2)-Essential-for-Life [L(2)EFL] Gene Family Modulates Dengue Virus Infection in Aedes aegypti.
Lucky R Runtuwene, Shuichi Kawashima, Victor D Pijoh, Josef S B Tuda, Kyoko Hayashida, Junya Yamagishi, Chihiro Sugimoto, Shoko Nishiyama, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa, Tomohiko Takasaki, Anthony A James, Takashi Kobayashi, Yuki Eshita
International journal of molecular sciences, 21, 20, 12 Oct. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Efforts to determine the mosquito genes that affect dengue virus replication have identified a number of candidates that positively or negatively modify amplification in the invertebrate host. We used deep sequencing to compare the differential transcript abundances in Aedes aegypti 14 days post dengue infection to those of uninfected A. aegypti. The gene lethal(2)-essential-for-life [l(2)efl], which encodes a member of the heat shock 20 protein (HSP20) family, was upregulated following dengue virus type 2 (DENV-2) infection in vivo. The transcripts of this gene did not exhibit differential accumulation in mosquitoes exposed to insecticides or pollutants. The induction and overexpression of l(2)efl gene products using poly(I:C) resulted in decreased DENV-2 replication in the cell line. In contrast, the RNAi-mediated suppression of l(2)efl gene products resulted in enhanced DENV-2 replication, but this enhancement occurred only if multiple l(2)efl genes were suppressed. l(2)efl homologs induce the phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the fruit fly Drosophila melanogaster, and we confirmed this finding in the cell line. However, the mechanism by which l(2)efl phosphorylates eIF2α remains unclear. We conclude that l(2)efl encodes a potential anti-dengue protein in the vector mosquito.

1940年代に日本国内において分離された狂犬病ウイルス株のゲノム解析　　　　　　　　　　　　　　　
犬飼 真秀, 高橋 龍樹, 佐々木 道仁, 藤井 祐至, Jarusombuti Supasiri, 西山 祥子, 澤 洋文, 杉山 誠, 伊藤 直人
日本獣医学会学術集会講演要旨集, 163回, 262, 262, (公社)日本獣医学会, Oct. 2020
Japanese

Discoveries of Exoribonuclease-Resistant Structures of Insect-Specific Flaviviruses Isolated in Zambia.
Christida E Wastika, Hayato Harima, Michihito Sasaki, Bernard M Hang'ombe, Yuki Eshita, Yongjin Qiu, William W Hall, Michael T Wolfinger, Hirofumi Sawa, Yasuko Orba
Viruses, 12, 9, 11 Sep. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, To monitor the arthropod-borne virus transmission in mosquitoes, we have attempted both to detect and isolate viruses from 3304 wild-caught female mosquitoes in the Livingstone (Southern Province) and Mongu (Western Province) regions in Zambia in 2017. A pan-flavivirus RT-PCR assay was performed to identify flavivirus genomes in total RNA extracted from mosquito lysates, followed by virus isolation and full genome sequence analysis using next-generation sequencing and rapid amplification of cDNA ends. We isolated a newly identified Barkedji virus (BJV Zambia) (10,899 nt) and a novel flavivirus, tentatively termed Barkedji-like virus (BJLV) (10,885 nt) from Culex spp. mosquitoes which shared 96% and 75% nucleotide identity with BJV which has been isolated in Israel, respectively. These viruses could replicate in C6/36 cells but not in mammalian and avian cell lines. In parallel, a comparative genomics screening was conducted to study evolutionary traits of the 5'- and 3'-untranslated regions (UTRs) of isolated viruses. Bioinformatic analyses of the secondary structures in the UTRs of both viruses revealed that the 5'-UTRs exhibit canonical stem-loop structures, while the 3'-UTRs contain structural homologs to exoribonuclease-resistant RNAs (xrRNAs), SL-III, dumbbell, and terminal stem-loop (3'SL) structures. The function of predicted xrRNA structures to stop RNA degradation by Xrn1 exoribonuclease was further proved by the in vitro Xrn1 resistance assay.

Avian Influenza Viruses Detected in Birds in Sub-Saharan Africa: A Systematic Review.
Annie Kalonda, Ngonda Saasa, Panji Nkhoma, Masahiro Kajihara, Hirofumi Sawa, Ayato Takada, Edgar Simulundu
Viruses, 12, 9, 07 Sep. 2020, [International Magazine]
English, Scientific journal, In the recent past, sub-Saharan Africa has not escaped the devastating effects of avian influenza virus (AIV) in poultry and wild birds. This systematic review describes the prevalence, spatiotemporal distribution, and virus subtypes detected in domestic and wild birds for the past two decades (2000-2019). We collected data from three electronic databases, PubMed, SpringerLink electronic journals and African Journals Online, using the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. A total of 1656 articles were reviewed, from which 68 were selected. An overall prevalence of 3.0% AIV in birds was observed. The prevalence varied between regions and ranged from 1.1% to 7.1%. The Kruskal-Wallis and Wilcoxon signed-rank sum test showed no significant difference in the prevalence of AIV across regions, χ2(3) = 5.237, p = 0.1553 and seasons, T = 820, z = -1.244, p = 0.2136. Nineteen hemagglutinin/neuraminidase subtype combinations were detected during the reviewed period, with southern Africa recording more diverse AIV subtypes than other regions. The most detected subtype was H5N1, followed by H9N2, H5N2, H5N8 and H6N2. Whilst these predominant subtypes were mostly detected in domestic poultry, H1N6, H3N6, H4N6, H4N8, H9N1 and H11N9 were exclusively detected in wild birds. Meanwhile, H5N1, H5N2 and H5N8 were detected in both wild and domestic birds suggesting circulation of these subtypes among wild and domestic birds. Our findings provide critical information on the eco-epidemiology of AIVs that can be used to improve surveillance strategies for the prevention and control of avian influenza in sub-Saharan Africa.

Co-Circulation of Multiple Serotypes of Bluetongue Virus in Zambia.
Herman M Chambaro, Michihito Sasaki, Edgar Simulundu, Isaac Silwamba, Yona Sinkala, Gabriel Gonzalez, David Squarre, Paul Fandamu, Caesar H Lubaba, Musso Munyeme, Alikhadio Maseko, Choopa Chimvwele, Liywalii Mataa, Lynnfield E Mooya, Andrew N Mukubesa, Hayato Harima, Kenny L Samui, Hetron M Munang'andu, Martin Simuunza, King S Nalubamba, Yongjin Qiu, Michael J Carr, William W Hall, Yuki Eshita, Hirofumi Sawa, Yasuko Orba
Viruses, 12, 9, 31 Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Bluetongue (BT) is an arthropod-borne viral disease of ruminants with serious trade and socio-economic implications. Although the disease has been reported in a number of countries in sub-Saharan Africa, there is currently no information on circulating serotypes and disease distribution in Zambia. Following surveillance for BT in domestic and wild ruminants in Zambia, BT virus (BTV) nucleic acid and antibodies were detected in eight of the 10 provinces of the country. About 40% (87/215) of pooled blood samples from cattle and goats were positive for BTV nucleic acid, while one hartebeest pool (1/43) was positive among wildlife samples. Sequence analysis of segment 2 revealed presence of serotypes 3, 5, 7, 12 and 15, with five nucleotypes (B, E, F, G and J) being identified. Segment 10 phylogeny showed Zambian BTV sequences clustering with Western topotype strains from South Africa, intimating likely transboundary spread of BTV in Southern Africa. Interestingly, two Zambian viruses and one isolate from Israel formed a novel clade, which we designated as Western topotype 4. The high seroprevalence (96.2%) in cattle from Lusaka and Central provinces and co-circulation of multiple serotypes showed that BT is widespread, underscoring the need for prevention and control strategies.

Genetic and Phenotypic Characterization of a Rabies Virus Strain Isolated from a Dog in Tokyo, Japan in the 1940s.
Tatsuki Takahashi, Maho Inukai, Michihito Sasaki, Madlin Potratz, Supasiri Jarusombuti, Yuji Fujii, Shoko Nishiyama, Stefan Finke, Kentaro Yamada, Hiroki Sakai, Hirofumi Sawa, Akira Nishizono, Makoto Sugiyama, Naoto Ito
Viruses, 12, 9, 20 Aug. 2020, [International Magazine]
English, Scientific journal, The rabies virus strain Komatsugawa (Koma), which was isolated from a dog in Tokyo in the 1940s before eradication of rabies in Japan in 1957, is known as the only existent Japanese field strain (street strain). Although this strain potentially provides a useful model to study rabies pathogenesis, little is known about its genetic and phenotypic properties. Notably, this strain underwent serial passages in rodents after isolation, indicating the possibility that it may have lost biological characteristics as a street strain. In this study, to evaluate the utility of the Koma strain for studying rabies pathogenesis, we examined the genetic properties and in vitro and in vivo phenotypes. Genome-wide genetic analyses showed that, consistent with previous findings from partial sequence analyses, the Koma strain is closely related to a Russian street strain within the Arctic-related phylogenetic clade. Phenotypic examinations in vitro revealed that the Koma strain and the representative street strains are less neurotropic than the laboratory strains. Examination by using a mouse model demonstrated that the Koma strain and the street strains are more neuroinvasive than the laboratory strains. These findings indicate that the Koma strain retains phenotypes similar to those of street strains, and is therefore useful for studying rabies pathogenesis.

Characterization of mammalian orthoreoviruses isolated from faeces of pigs in Zambia.
Hayato Harima, Michihito Sasaki, Masahiro Kajihara, Gabriel Gonzalez, Edgar Simulundu, Eugene C Bwalya, Yongjin Qiu, Kosuke Okuya, Mao Isono, Yasuko Orba, Ayato Takada, Bernard M Hang'ombe, Aaron S Mweene, Hirofumi Sawa
The Journal of general virology, 101, 10, 1027, 1036, 24 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Mammalian orthoreovirus (MRV) has been identified in humans, livestock and wild animals; this wide host range allows individual MRV to transmit into multiple species. Although several interspecies transmission and genetic reassortment events of MRVs among humans, livestock and wildlife have been reported, the genetic diversity and geographic distribution of MRVs in Africa are poorly understood. In this study, we report the first isolation and characterization of MRVs circulating in a pig population in Zambia. In our screening, MRV genomes were detected in 19.7 % (29/147) of faecal samples collected from pigs by reverse transcription PCR. Three infectious MRV strains (MRV-85, MRV-96 and MRV-117) were successfully isolated, and their complete genomes were sequenced. Recombination analyses based on the complete genome sequences of the isolated MRVs demonstrated that MRV-96 shared the S3 segment with a different MRV isolated from bats, and that the L1 and M3 segments of MRV-117 originated from bat and human MRVs, respectively. Our results suggest that the isolated MRVs emerged through genetic reassortment events with interspecies transmission. Given the lack of information regarding MRVs in Africa, further surveillance of MRVs circulating among humans, domestic animals and wildlife is required to assess potential risk for humans and animals.

Isolation of Candidatus Bartonella rousetti and Other Bat-associated Bartonellae from Bats and Their Flies in Zambia.
Yongjin Qiu, Masahiro Kajihara, Ryo Nakao, Evans Mulenga, Hayato Harima, Bernard Mudenda Hang'ombe, Yoshiki Eto, Katendi Changula, Daniel Mwizabi, Hirofumi Sawa, Hideaki Higashi, Aaron Mweene, Ayato Takada, Martin Simuunza, Chihiro Sugimoto
Pathogens (Basel, Switzerland), 9, 6, 13 Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Bat-associated bartonellae, including Bartonella mayotimonensis and Candidatus Bartonella rousetti, were recently identified as emerging and potential zoonotic agents, respectively. However, there is no report of bat-associated bartonellae in Zambia. Thus, we aimed to isolate and characterize Bartonella spp. from bats and bat flies captured in Zambia by culturing and PCR. Overall, Bartonella spp. were isolated from six out of 36 bats (16.7%), while Bartonella DNA was detected in nine out of 19 bat flies (47.3%). Subsequent characterization using a sequence of five different genes revealed that three isolates obtained from Egyptian fruit bats (Rousettus aegyptiacus) were Ca. B. rousetti. The isolates obtained from insectivorous bats (Macronycteris vittatus) were divided into two previously unclassified bat-associated bartonellae. A phylogenetic analysis of the six genotypes of Bartonella gltA sequences from nine pathogen-positive bat flies revealed that three genotypes belonged to the same clades as bat-associated bartonellae, including Ca. B. rousetti. The other three genotypes represented arthropod-associated bartonellae, which have previously been isolated only from ectoparasites. We demonstrated that Ca. B. rousetti is maintained between bats (R. aegyptiacus) and bat flies in Zambia. Continuous surveillance of Bartonella spp. in bats and serological surveys in humans in Africa are warranted to evaluate the public health importance of bat-associated bartonellae.

Host ESCRT factors are recruited during chikungunya virus infection and are required for the intracellular viral replication cycle.
Shiho Torii, Yasuko Orba, Michihito Sasaki, Koshiro Tabata, Yuji Wada, Michael Carr, Jody Hobson-Peters, Roy A Hall, Ayato Takada, Takasuke Fukuhara, Yoshiharu Matsuura, William W Hall, Hirofumi Sawa
The Journal of biological chemistry, 295, 23, 7941, 7957, 05 Jun. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Chikungunya fever is a re-emerging zoonotic disease caused by chikungunya virus (CHIKV), a member of the Alphavirus genus in the Togaviridae family. Only a few studies have reported on the host factors required for intracellular CHIKV trafficking. Here, we conducted an imaging-based siRNA screen to identify human host factors for intracellular trafficking that are involved in CHIKV infection, examined their interactions with CHIKV proteins, and investigated the contributions of these proteins to CHIKV infection. The results of the siRNA screen revealed that host endosomal sorting complexes required for transport (ESCRT) proteins are recruited during CHIKV infection. Co-immunoprecipitation analyses revealed that both structural and nonstructural CHIKV proteins interact with hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a component of the ESCRT-0 complex. We also observed that HGS co-localizes with the E2 protein of CHIKV and with dsRNA, a marker of the replicated CHIKV genome. Results from gene knockdown analyses indicated that, along with other ESCRT factors, HGS facilitates both genome replication and post-translational steps during CHIKV infection. Moreover, we show that ESCRT factors are also required for infections with other alphaviruses. We conclude that during CHIKV infection, several ESCRT factors are recruited via HGS and are involved in viral genome replication and post-translational processing of viral proteins.

Evidence for exposure of asymptomatic domestic pigs to African Swine fever virus during an inter-epidemic period in Zambia.
Herman M Chambaro, Michihito Sasaki, Yona Sinkala, Gabriel Gonzalez, David Squarre, Paul Fandamu, Caesar Lubaba, Liywalii Mataa, Misheck Shawa, Kabemba E Mwape, Sarah Gabriël, Mwelwa Chembensofu, Michael J Carr, William W Hall, Yongjin Qiu, Masahiro Kajihara, Ayato Takada, Yasuko Orba, Edgar Simulundu, Hirofumi Sawa
Transboundary and emerging diseases, 67, 6, 2741, 2752, 20 May 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, African swine fever (ASF) causes persistent outbreaks in endemic and non-endemic regions in Zambia. However, the epidemiology of the disease is poorly understood, particularly during the inter-epidemic periods. We conducted surveillance for ASF in asymptomatic domestic pigs and soft ticks in selected Zambian provinces. Whilst serum samples (n=1,134) were collected from crossbred pigs from all study sites between 2014 and 2017, whole blood (n=300) was collected from both crossbred and indigenous pigs in Eastern Province (EP) in 2017. Soft ticks were collected from Mosi-oa-Tunya National Park in Southern Province (SP) in 2019. Sera were screened for antibodies against ASF by ELISA while genome detection in whole blood and soft ticks was conducted by PCR. Ticks were identified morphologically and by phylogenetic analysis of the 16S rRNA gene. Seroprevalence was highest in EP (50.9%, 95% CI [47.0 - 54.9]) compared to significantly lower rates in SP (2.9%, 95% CI [1.6 - 5.1]). No antibodies to ASFV were detected in Lusaka Province. In EP, the prevalence of ASFV genome was 11.7% (35/300), significantly higher (OR = 6.2, 95% CI [2.4 - 16.6]) in indigenous pigs compared to crossbred pigs. The pooled prevalence of ASFV genome in ticks was 11.0%, 95% CI [8.5-13.9]. Free-range husbandry system was the only factor that was significantly associated with seropositive (p < 0.0001, OR = 39.3) and PCR positive results (p < 0.001, OR = 5.7). Phylogenetically, based on the p72 gene, ASFV from Ornithodoros moubata ticks detected in this study belonged to genotype I, but they separated into two distinct clusters. Besides confirming ASF endemicity in EP and the presence of ASFV-infected ticks in SP, these results provide evidence for exposure of domestic pigs to ASFV in non-endemic regions during the inter-epidemic period.

Amino acid 159 of the envelope protein affects viral replication and T-cell infiltration by West Nile virus in intracranial infection.
Shintaro Kobayashi, Chisato Kaneko, Ryoko Kawakami, Rie Hasebe, Hirofumi Sawa, Kentaro Yoshii, Hiroaki Kariwa
Scientific reports, 10, 1, 7168, 7168, 28 Apr. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, West Nile virus (WNV) is an important cause of viral encephalitis in birds and animals, including humans. Amino acid 159 of the envelope (E) protein is reportedly implicated in the different levels of neurovirulence in mice infected with WNV NY99 or Eg101. We investigated the role of amino acid 159 of the E protein in the pathogenesis of WNV infection. We produced recombinant WNV with the structural proteins of the NY99 or Eg101 strain (NY-WT or EgCME-WT) and mutant viruses with substitutions of amino acid 159 of the E protein (NY-E-V159I or EgCME-E-I159V). The NY-WT and NY-E-V159I or EgCME-WT and EgCME-E-I159V titers in culture supernatant were similar. The mortality rate and viral titer in the brains of mice inoculated intraperitoneally with NY-WT or NY-E-V159I were also similar. In contrast, the mortality rate and viral titer in the brains of mice inoculated intracranially with EgCME-E-I159V were significantly higher than those of mice inoculated with EgCME-WT. The numbers of CD3-positive and CD8-positive T cells were greater in brains inoculated with EgCME-E-I159V than in those inoculated with EgCME-WT. Therefore, amino acid 159 of the E protein modulates the pathogenicity of WNV by affecting viral replication and T-cell infiltration in the brain.

Interferon lambda rs368234815 ΔG/ΔG is associated with higher CD4+:CD8+ T-cell ratio in treated HIV-1 infection.
Inês T Freitas, Willard Tinago, Hirofumi Sawa, Julie McAndrews, Brenda Doak, Charlotte Prior-Fuller, Gerard Sheehan, John S Lambert, Eavan Muldoon, Aoife G Cotter, William W Hall, Patrick W G Mallon, Michael J Carr
AIDS research and therapy, 17, 1, 13, 13, 15 Apr. 2020, [International Magazine]
English, Scientific journal, BACKGROUND: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. METHODS: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L-(effector-memory) and CD45RO-CD62L+ (naïve), using logistic and linear regression models, respectively. RESULTS: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39-48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7-10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: - 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). CONCLUSIONS: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH.

West Nile Virus in Farmed Crocodiles, Zambia, 2019.
Edgar Simulundu, Kunda Ndashe, Herman M Chambaro, David Squarre, Paul Michael Reilly, Simbarashe Chitanga, Katendi Changula, Andrew N Mukubesa, Joseph Ndebe, John Tembo, Nathan Kapata, Matthew Bates, Yona Sinkala, Bernard M Hang'ombe, King S Nalubamba, Masahiro Kajihara, Michihito Sasaki, Yasuko Orba, Ayato Takada, Hirofumi Sawa
Emerging infectious diseases, 26, 4, 811, 814, Apr. 2020, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, We detected West Nile virus (WNV) nucleic acid in crocodiles (Crocodylus niloticus) in Zambia. Phylogenetically, the virus belonged to lineage 1a, which is predominant in the Northern Hemisphere. These data provide evidence that WNV is circulating in crocodiles in Africa and increases the risk for animal and human transmission.

Genetic and Biological Diversity of Porcine Sapeloviruses Prevailing in Zambia.
Hayato Harima, Masahiro Kajihara, Edgar Simulundu, Eugene Bwalya, Yongjin Qiu, Mao Isono, Kosuke Okuya, Gabriel Gonzalez, Junya Yamagishi, Bernard M Hang'ombe, Hirofumi Sawa, Aaron S Mweene, Ayato Takada
Viruses, 12, 2, 05 Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Porcine sapelovirus (PSV) has been detected worldwide in pig populations. Although PSV causes various symptoms such as encephalomyelitis, diarrhea, and pneumonia in pigs, the economic impact of PSV infection remains to be determined. However, information on the distribution and genetic diversity of PSV is quite limited, particularly in Africa. In this study, we investigated the prevalence of PSV infection in Zambia and characterized the isolated PSVs genetically and biologically. We screened 147 fecal samples collected in 2018 and found that the prevalences of PSV infection in suckling pigs and fattening pigs were high (36.2% and 94.0%, respectively). Phylogenetic analyses revealed that the Zambian PSVs were divided into three different lineages (Lineages 1-3) in the clade consisting of Chinese strains. The Zambian PSVs belonging to Lineages 2 and 3 replicated more efficiently than those belonging to Lineage 1 in Vero E6 and BHK cells. Bioinformatic analyses revealed that genetic recombination events had occurred and the recombination breakpoints were located in the L and 2A genes. Our results indicated that at least two biologically distinct PSVs could be circulating in the Zambian pig population and that genetic recombination played a role in the evolution of PSVs.

Detection of novel orthoreovirus genomes in shrew (Crocidura hirta) and fruit bat (Rousettus aegyptiacus).
Hayato Harima, Michihito Sasaki, Masahiro Kajihara, Akina Mori-Kajihara, Bernard M Hang'ombe, Katendi Changula, Yasuko Orba, Hirohito Ogawa, Martin Simuunza, Reiko Yoshida, Aaron Mweene, Ayato Takada, Hirofumi Sawa
The Journal of veterinary medical science, 82, 2, 162, 167, 04 Feb. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Orthoreoviruses have been indentified in several mammals, however, there is no information about orthoreoviruses in shrews. In this study, we screened wild animals in Zambia, including shrews, rodents, and bats for the detection of orthoreoviruses. Two orthoreovirus RNA genomes were detected from a shrew intestinal-contents (1/24) and a bat colon (1/96) sample by reverse-transcription (RT)-PCR targeting the RNA-dependent RNA polymerase gene of orthoreoviruses. Phylogenetic analyses revealed that each of the identified orthoreoviruses formed a distinct branch among members of the Orthoreovirus genus. This is the first report that shrews are susceptible to orthoreovirus infection. Our results suggest the existence of undiscovered orthoreoviruses in shrews and provide important information about the genetic diversity of orthoreoviruses.

北海道における新規オルソナイロウイルス(エゾウイルス:Yezo virus)によるマダニ媒介性急性発熱性疾患の発見　　　　　　　　　　　　　　　
児玉 文宏, 枝川 峻二, 永坂 敦, 松野 啓太, 好井 健太朗, 澤 洋文, 山岸 彩沙, 古澤 弥, 山口 亮, 矢野 公一, 山口 宏樹, 後藤 明子, 駒込 理佳, 三好 正浩, 伊東 拓也, 小山内 佑太, 角 千春, 堀田 明豊, 前田 健, 安藤 秀二, 西條 政幸
病原微生物検出情報月報, 41, 1, 11, 13, 国立感染症研究所, Jan. 2020
Japanese

生体防御 Fitness costによって誘導されるP.aeruginosa変異株のファージ感受性トレードオフ　　　　　　　　　　　　　　　
藤木 純平, マンビ・モンゴメリ, 中村 暢宏, 権平 智, 佐々木 道仁, 臼井 優, 樋口 豪紀, 澤 洋文, 田村 豊, 岩野 英知
日本細菌学雑誌, 75, 1, 57, 57, 日本細菌学会, Jan. 2020
Japanese

West Nile virus capsid protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development.
Shintaro Kobayashi, Kentaro Yoshii, Wallaya Phongphaew, Memi Muto, Minato Hirano, Yasuko Orba, Hirofumi Sawa, Hiroaki Kariwa
PLoS pathogens, 16, 1, e1008238, Jan. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, West Nile virus (WNV) belongs to the Flaviviridae family and has emerged as a significant cause of viral encephalitis in birds and animals including humans. WNV replication directly induces neuronal injury, followed by neuronal cell death. We previously showed that accumulation of ubiquitinated protein aggregates was involved in neuronal cell death in the WNV-infected mouse brain. In this study, we attempted to elucidate the mechanisms of the accumulation of protein aggregates in the WNV-infected cells. To identify the viral factor inducing the accumulation of ubiquitinated proteins, intracellular accumulation of ubiquitinated proteins was examined in the cells expressing the viral protein. Expression of capsid (C) protein induced the accumulation, while mutations at residues L51 and A52 in C protein abrogated the accumulation. Wild-type (WT) or mutant WNV in which mutations were introduced into the residues was inoculated into human neuroblastoma cells. The expression levels of LC3-II, an autophagy-related protein, and AMP-activated protein kinase (AMPK), an autophagy inducer, were reduced in the cells infected with WT WNV, while the reduction was not observed in the cells infected with WNV with the mutations in C protein. Similarly, ubiquitination and degradation of AMPK were only observed in the cells infected with WT WNV. In the cells expressing C protein, AMPK was co-precipitated with C protein and mutations in L51 and A52 reduced the interaction. Although the viral replication was not affected, the accumulation of ubiquitinated proteins in brain and neurological symptoms were attenuated in the mouse inoculated with WNV with the mutations in C protein as compared with that with WT WNV. Taken together, ubiquitination and degradation of AMPK by C protein resulted in the inhibition of autophagy and the accumulation of protein aggregates, which contributes to the development of neurological disease.

Inhibition of dengue virus infection by 1-stearoyl-2-arachidonoyl-phosphatidylinositol in vitro.
Takao Sanaki, Masato Wakabayashi, Takeshi Yoshioka, Ryu Yoshida, Takao Shishido, William W Hall, Hirofumi Sawa, Akihiko Sato
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33, 12, 13866, 13881, Dec. 2019, [International Magazine]
English, Scientific journal, Dengue fever is an acute febrile infectious disease caused by dengue virus (DENV). Despite the significant public health concerns posed by DENV, there are currently no effective anti-DENV therapeutic agents. To develop such drugs, a better understanding of the detailed mechanisms of DENV infection is needed. Both lipid metabolism and lipid synthesis are activated in DENV-infected cells, so we used lipid screening to identify potential antiviral lipid molecules. We identified 1-stearoyl-2-arachidonoyl-phosphatidylinositol (SAPI), which is the most abundant endogenous phosphatidylinositol (PI) molecular species, as an anti-DENV lipid molecule. SAPI suppressed the cytopathic effects induced by DENV2 infection as well as the replication of all DENV serotypes without inhibiting the entry of DENV2 into host cells. However, no other PI molecular species or PI metabolites, including lysophosphatidylinositols and phosphoinositides, displayed anti-DENV2 activity. Furthermore, SAPI suppressed the production of DENV2 infection-induced cytokines and chemokines, including C-C motif chemokine ligand (CCL)5, CCL20, C-X-C chemokine ligand 8, IL-6, and IFN-β. SAPI also suppressed the TNF-α production induced by LPS stimulation in macrophage cells differentiated from THP-1 cells. Our results demonstrated that SAPI is an endogenous inhibitor of DENV and modulated inflammatory responses in DENV2-infected cells, at least in part via TLR 4.-Sanaki, T., Wakabayashi, M., Yoshioka, T., Yoshida, R., Shishido, T., Hall, W. W., Sawa, H., Sato, A. Inhibition of dengue virus infection by 1-stearoyl-2-arachidonoyl-phosphatidylinositol in vitro.

Neo-virology: The raison d'etre of viruses
Tokiko Watanabe, Nobuhiro Suzuki, Keizo Tomonaga, Hirofumi Sawa, Yoshiharu Matsuura, Yasushi Kawaguchi, Hideki Takahashi, Keizo Nagasaki, Yoshihiro Kawaoka
Virus Research, 274, 197751, 197751, Dec. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal

Seroprevalence of Rift Valley fever in cattle of smallholder farmers in Kwilu Province in the Democratic Republic of Congo.
Abdel-Amir Dib Halawi, Ngonda Saasa, Boniface Lombe Pongombo, Masahiro Kajihara, Herman Moses Chambaro, Mutambel Hity, Hirofumi Sawa, Ayato Takada, Aaron S Mweene, Luamba Lua Nsembo, Edgar Simulundu
Tropical animal health and production, 51, 8, 2619, 2627, Nov. 2019, [International Magazine]
English, Scientific journal, Rift Valley fever (RVF) is a zoonotic mosquito-borne disease caused by RVF virus (RVFV) that causes abortions and high mortalities in livestock and is also associated with acute and fatal disease in humans. In the Democratic Republic of Congo (DRC), information on the epidemiology of RVF is limited, particularly among cattle reared by smallholder farmers. This cross-sectional study was conducted to investigate the seroprevalence of RVF in cattle raised by smallholder farmers in Kwilu Province of DRC, which has not yet reported an RVF epidemic. A total of 677 cattle sera were collected from four territories and tested for anti-RVFV antibodies using immunofluorescent assay and enzyme-linked immunosorbent assay. The overall seroprevalence of anti-RVFV IgG was 6.5% (44/677) (95% CI 4.81-8.7). There was a statistically significant difference in the seroprevalence among the territories (χ2 = 28.79, p < 0.001). Territory seroprevalences were as follows: Idiofa 14.08% (95% CI 9.78-19.76), Bulungu 4.14% (95% CI 1.83-8.68), Gungu 3.21% (95% CI 1.41-6.78), and Masi-Manimba 1.19% (95% CI 0.06-7.37). Seroprevalence differed significantly among age categories (p = 0.0017) and ecosystem (p < 0.001). The seroprevalence of animals aged between 1 and 2 years was 20.0% (95% CI 8.4-39.13) and was higher than group aged <1 year, between 2 and 3 years, and > 3 years. Forest area (18.92% (95% CI 12.35-27.7)) had higher seropositivity than savannah area (4.06% (95% CI 2.65-6.12)). Sex difference was not significant (χ2 = 0.14, p = 0.704). These findings indicate that cattle in Kwilu Province had been exposed to RVFV, which represents a significant risk for both livestock and human health.

Genetic diversity of rabies virus in different host species and geographic regions of Zambia and Zimbabwe.
Muleya W, Chambaro HM, Sasaki M, Gwenhure LF, Mwenechanya R, Kajihara M, Saasa N, Mupila Z, Mori-Kajihara A, Qiu Y, Kangwa E, Mweene A, Namangala B, Takada A, Sawa H
Virus genes, 55, 5, 713, 719, Oct. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Rabies is endemic in Zambia and Zimbabwe. The previously investigated strains of rabies virus in central Zambia belong to the Africa 1b lineage, with similar circulating virus strains found in the various tested hosts and regions. However, prior work assessed only limited regions and host species. Thus, this study aimed to more comprehensively determine the genetic diversity of rabies virus across regions of Zambia and Zimbabwe. RNA (n = 76) was extracted from positive direct fluorescent antibody test brain tissues from dog, cow, goat, cat, pig, human, and jackal collected from Zambia and Zimbabwe. The amplicons of the nucleoprotein and glycoprotein genes were obtained from all examined samples by nested RT-PCR and subsequently sequenced. A phylogenetic analysis of the N gene confirmed that all the endemic strains of rabies virus in Zambia and Zimbabwe belong to the Africa 1b lineage. The obtained viral gene sequences were phylogenetically divided into two clusters. Cluster II comprised only Zambian strains. In contrast, cluster I comprised both Zambia and Zimbabwe strains, with strains from Zimbabwe forming a distinct lineage from Zambian strains, implying viral genetic divergence due to geographical barriers. However, no evidence of clustering based on host or region was observed, implying the circulation of similar virus strains occurs in different hosts and regions of Zambia and Zimbabwe. The clustering of rabies virus strains from jackals with those from domestic animals provides evidence of similar virus strains circulating in both wildlife and domestic animals, and that the jackal might be one of the potential reservoirs of rabies virus infection. In this study, no strains circulating in Zimbabwe were detected in Zambia.

Upregulated expression of the antioxidant sestrin 2 identified by transcriptomic analysis of Japanese encephalitis virus-infected SH-SY5Y neuroblastoma cells.
Carr M, Gonzalez G, Martinelli A, Wastika CE, Ito K, Orba Y, Sasaki M, Hall WW, Sawa H
Virus genes, 55, 5, 630, 642, Oct. 2019, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Japanese encephalitis virus (JEV) exerts a profound burden of viral encephalitis. We have investigated the differentially expressed transcripts in the neuronal transcriptome during JEV infection by RNA sequencing (RNA-Seq) of virus-infected SH-SY5Y human neuroblastoma cells. Gene ontology analysis revealed significant enrichment from two main pathways: endoplasmic reticulum (ER)-nucleus signaling (P value: 5.75E-18; false discovery rate [FDR] 3.11E-15) and the ER unfolded protein response (P value: 7.58E-18; FDR 3.11E-15). qPCR validation showed significant upregulation and differential expression (P < 0.01) of ER stress-signaling transcripts (SESN2, TRIB3, DDIT3, DDIT4, XBP1, and ATF4) at 24 h post-infection for both low (LN) and high (HN) neurovirulence JEV strains. Immunoblot analysis following JEV infection of SH-SY5Y cells showed an increase in levels of SESN2 protein following JEV infection. Similarly, Zika virus (MR766) infection of SH-SY5Y showed a titer-dependent increase in ER stress-signaling transcripts; however, this was absent or diminished for DDIT4 and ATF4, respectively, suggestive of differences in the induction of stress-response transcripts between flaviviruses. Interestingly, SLC7A11 and SLC3A2 mRNA were also both deregulated in JEV-infected SH-SY5Y cells and encode the two constituent subunits of the plasma membrane xCT amino acid antiporter that relieves oxidative stress by export of glutamate and import of cystine. Infection of SH-SY5Y and HEK293T cells by the JEV HN strain Sw/Mie/40/2004 lead to significant upregulation of the SLC7A11 mRNA to levels comparable to DDIT3. Our findings suggest upregulation of antioxidants including SESN2 and, also, the xCT antiporter occurs to counteract the oxidative stress elicited by JEV infection.

Autopsy findings in the early stage of amyotrophic lateral sclerosis with "dropped head" syndrome.
Tanikawa S, Tanino M, Wang L, Ishikawa M, Miyazaki M, Tsuda M, Orba Y, Sawa H, Matoba K, Nakamura N, Nagashima K, Hall WW, Tanaka S
Neuropathology : official journal of the Japanese Society of Neuropathology, 39, 5, 374, 377, Oct. 2019, [Peer-reviewed]

狂犬病ウイルスの増殖におけるL蛋白質NPYNE配列の重要性　　　　　　　　　　　　　　　
牧野 真知子, 伊藤 直人, 中川 賢人, 佐々木 道仁, 高橋 龍樹, 岡田 和真, 西山 祥子, 澤 洋文, 杉山 誠
日本獣医学会学術集会講演要旨集, 162回, 432, 432, (公社)日本獣医学会, Aug. 2019
Japanese

Marburgvirus in Egyptian Fruit Bats, Zambia.
Kajihara M, Hang'ombe BM, Changula K, Harima H, Isono M, Okuya K, Yoshida R, Mori-Kajihara A, Eto Y, Orba Y, Ogawa H, Qiu Y, Sawa H, Simulundu E, Mwizabi D, Munyeme M, Squarre D, Mukonka V, Mweene A, Takada A
Emerging infectious diseases, 25, 8, 1577, 1580, Aug. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, We detected Marburg virus genome in Egyptian fruit bats (Rousettus aegyptiacus) captured in Zambia in September 2018. The virus was closely related phylogenetically to the viruses that previously caused Marburg outbreaks in the Democratic Republic of the Congo. This finding demonstrates that Zambia is at risk for Marburg virus disease.

Publisher Correction: Discovery and genetic characterization of diverse smacoviruses in Zambian non-human primates.
Anindita PD, Sasaki M, Gonzalez G, Phongphaew W, Carr M, Hang'ombe BM, Mweene AS, Ito K, Orba Y, Sawa H
Scientific reports, 9, 1, 8502, 8502, Jun. 2019, [Peer-reviewed], [Last author], [International Magazine]
English, A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Field diagnosis and genotyping of chikungunya virus using a dried reverse transcription loop-mediated isothermal amplification (LAMP) assay and MinION sequencing.
Hayashida K, Orba Y, Sequeira PC, Sugimoto C, Hall WW, Eshita Y, Suzuki Y, Runtuwene L, Brasil P, Calvet G, Rodrigues CDS, Santos CCD, Mares-Guia MAM, Yamagishi J, Filippis AMB, Sawa H
PLoS neglected tropical diseases, 13, 6, e0007480, Jun. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Detection and sequencing of chikungunya virus (CHIKV) genome was performed using a combination of a modified reverse transcription loop-mediated isothermal amplification (RT-LAMP) method and a MinION sequencer. We developed the protocol for drying all the reagents for the RT-LAMP in a single reaction tube. Using this system, the CHIKV genome was effectively amplified under isothermal conditions, and used as a template for MinION sequencing with a laptop computer. Our in-house RT-LAMP method and MinION sequencing system were also validated with RNAs and serum samples from recent outbreaks of CHIKV patients in Brazil. The obtained sequence data confirmed the CHIKV outbreaks and identified the genotype. In summary, our established inexpensive on-site genome detection and sequencing system is applicable for both diagnosis of CHIKV infected patients and genotyping of the CHIKV virus in future outbreak in remote areas.

Serological evidence of Zika virus infection in non-human primates in Zambia.
Wastika CE, Sasaki M, Yoshii K, Anindita PD, Hang'ombe BM, Mweene AS, Kobayashi S, Kariwa H, Carr MJ, Hall WW, Eshita Y, Orba Y, Sawa H
Archives of virology, 164, 8, 2165, 2170, Jun. 2019, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Zika virus (ZIKV) circulation occurs between non-human primates (NHPs) in a sylvatic transmission cycle. To investigate evidence of flavivirus infection in NHPs in Zambia, we performed a plaque reduction neutralization test (PRNT) to quantify neutralizing antibodies. PRNT revealed that sera from NHPs (African green monkeys and baboons) exhibited neutralizing activity against ZIKV (34.4%; 33/96), whereas a PRNT for yellow fever virus using NHP sera showed no neutralization activity. ZIKV genomic RNA was not detected in splenic tissues from NHPs, suggesting that the presence of anti-ZIKV neutralizing antibodies represented resolved infections. Our evidence suggests that ZIKV is maintained in NHP reservoirs in Zambia.

Human borreliosis caused by a New World relapsing fever Borrelia-like organism in the Old World.　　　　　　　　　　　　　　　
Qiu Y, Nakao R, Hang’ombe BM, Sato K, Kajihara M, Kanchela S, Changula K, Eto Y, Ndebe J, Sasaki M, Thu MJ, Takada A, Sawa H, Sugimoto C, Kawabata H
Clinical Infectious Diseases, 69, 1, 107, 112, Jun. 2019, [Peer-reviewed]
English, Scientific journal

Discovery and genetic characterization of diverse smacoviruses in Zambian non-human primates.
Anindita PD, Sasaki M, Gonzalez G, Phongphaew W, Carr M, Hang'ombe BM, Mweene AS, Ito K, Orba Y, Sawa H
Scientific reports, 9, 1, 5045, 5045, Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The Smacoviridae has recently been classified as a family of small circular single-stranded DNA viruses. An increasing number of smacovirus genomes have been identified exclusively in faecal matter of various vertebrate species and from insect body parts. However, the genetic diversity and host range of smacoviruses remains to be fully elucidated. Herein, we report the genetic characterization of eleven circular replication-associated protein (Rep) encoding single-stranded (CRESS) DNA viruses detected in the faeces of Zambian non-human primates. Based on pairwise genome-wide and amino acid identities with reference smacovirus species, ten of the identified CRESS DNA viruses are assigned to the genera Porprismacovirus and Huchismacovirus of the family Smacoviridae, which bidirectionally encode two major open reading frames (ORFs): Rep and capsid protein (CP) characteristic of a type IV genome organization. The remaining unclassified CRESS DNA virus was related to smacoviruses but possessed a genome harbouring a unidirectionally oriented CP and Rep, assigned as a type V genome organization. Moreover, phylogenetic and recombination analyses provided evidence for recombination events encompassing the 3'-end of the Rep ORF in the unclassified CRESS DNA virus. Our findings increase the knowledge of the known genetic diversity of smacoviruses and highlight African non-human primates as carrier animals.

Molecular characterization and phylogenetic analysis of Trypanosoma spp. isolated from striped leaf-nosed bat (Hipposideros vittatus) in Zambia.
Qiu Y, Simuunza M, Mwizabi D, Changula K, Harima H, Takada A, Kajihara M, Takadate Y, Nakao R, Kawabata H, Sugimoto C, Mweene A, Sawa H, Eto Y, Mudenda Hang’ombe B, Hayashida K, Yoshida R, Mori-Kajihara A, Ndebe J
International Journal for Parasitology, 9, 234, 238, Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Bat trypanosomes consist of more than 30 trypanosome species from over 70 species of bats. Recent studies suggest that bats play a role in disseminating trypanosomes from African continent to the terrestrial mammals both in the Afrotropic-Palearctic Ecozones and Nearctic Ecozone. However, the diversity, distribution, and evolution of bat trypanosomes are still unclear. To better understand their evolution, more genetic data of bat trypanosomes from a variety of locations are required. During a survey of Borrelia spp. of bats inhabiting a cave in Zambia, we observed flagellate parasites from 5 of 43 hemocultures. Sequence and phylogenetic analyses of the glycosomal glyceraldehyde 3-phosphate dehydrogenase gene (gGAPDH; 572 bp) and the 18S ribosomal RNA gene (18S rRNA gene; 1,079-1,091 bp) revealed that all were Trypanosoma spp. belonged to the Trypanosoma cruzi clade. Three and two of them exhibited the similarity with T. conorhini and T. dionisii, respectively. The present study provides the first genetic data on Trypanosoma spp. of bats inhabiting Zambia.

A novel combination of prion strain co-occurrence in patients with sporadic Creutzfeldt-Jakob disease.
Kobayashi A, Iwasaki Y, Takao M, Saito Y, Iwaki T, Qi Z, Torimoto R, Shimazaki T, Munesue Y, Isoda N, Sawa H, Aoshima K, Kimura T, Kondo H, Mohri S, Kitamoto T
The American journal of pathology, 189, 6, 1276, 1283, Mar. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathologic features, genotype at polymorphic codon 129 [methionine (M)/valine (V)] of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathologic features and the coexistence of two types of abnormal prion proteins in the same patient also have been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathologic characteristics of the MM2 thalamic form (ie, neuronal loss of the inferior olivary nucleus of the medulla). Furthermore, coexistence of biochemical features of the MM2 thalamic form also was confirmed in the identified cases. In addition, in transmission experiments using prion protein-humanized mice, the brain material from the identified case showed weak infectivity and generated characteristic abnormal prion proteins in the inoculated mice resembling those after inoculation with brain material of MM2 thalamic form. Taken together, these results show that the co-occurrence of MM1 and MM2 thalamic form is a novel entity of sporadic Creutzfeldt-Jakob disease prion strain co-occurrence. The present study raises the possibility that the co-occurrence of the MM2 thalamic form might have been overlooked so far because of the scarcity of abnormal prion protein accumulation and restricted neuropathology.

Infection of newly identified phleboviruses in ticks and wild animals in Hokkaido, Japan indicating tick-borne life cycles.
Shiho Torii, Keita Matsuno, Yongjin Qiu, Akina Mori-Kajihara, Masahiro Kajihara, Ryo Nakao, Naganori Nao, Katsunori Okazaki, Mariko Sashika, Takahiro Hiono, Masatoshi Okamatsu, Yoshihiro Sakoda, Hideki Ebihara, Ayato Takada, Hirofumi Sawa
Ticks and tick-borne diseases, 10, 2, 328, 335, Feb. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Recent discoveries of tick-borne pathogens have raised public health concerns on tick-borne infectious diseases and emphasize the need to assess potential risks of unrecognized tick-borne pathogens. First, to determine the existence of tick-borne phleboviruses (TBPVs), genetic surveillance of phleboviruses in ticks was conducted mainly in Hokkaido, the northernmost island in Japan from 2013 to 2015. Genes of two TBPVs, previously reported as Mukawa virus (MKWV) and a newly identified relative of MKWV, Kuriyama virus (KURV), were detected and the viruses were isolated from Ixodes persulcatus collected in Hokkaido, but not in I. persulcatus collected from other areas of Japan. These viruses were phylogenetically and antigenically similar to each other. Next, to investigate the infection of MKWV in mammals, serum samples from wildlife captured in Hokkaido from 2007 to 2011 were used for serological screening. Neutralizing antibodies against MKWV were detected in both Yezo-deer (Cervus nippon yesoensis) (2/50) and raccoons (Procyon lotor) (16/64). However, no infectious MKWV was recovered from laboratory mice in experimental infections, though viral RNAs were detected in their tissues. Thus, MKWV and KURV may maintain tick-mammalian life cycles in Hokkaido, suggesting their potential as causative agents of tick-borne diseases in mammals.

"Integrated diagnosis" of pilocytic astrocytoma: Molecular diagnostic procedure for an unusual case.
Ishida Y, Tsuda M, Sawamura Y, Fujii K, Murai H, Horiuchi N, Orba Y, Sawa H, Hall WW, Nagashima K, Tanaka S
Pathology international, 68, 12, 694, 699, Dec. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, A 24 year-old female presented with a mass lesion in the right temporal lobe. This case was difficult to diagnose using histological and immunological methods and therefore molecular analyses were applied to provide a definitive diagnosis. The tumor was well-demarcated, partially cystic, and irregularly-enhanced on gadolinium-enhanced T1-weighted magnetic resonance images. Pathologically, a large part of the tumor consisted of cells with fine cytoplasmic processes on a myxoid and mucinous background. Cells formed a microcystic structure around the mucinous tissue. Numerous eosinophilic granular bodies, but not Rosenthal fibers, were present. The solid and compact regions of the tumor were composed of fasciculation of dense fibrous glial tissues and occasional multinucleated giant cells. Tumor cells and their fragmented cytoplasmic processes were positively stained with GFAP, while eosinophilic granular bodies were both positive and negative. Xanthomatous changes were not detected and the reticulin fibers were restricted to vascular tissues. The MIB1 index was scored as approximately 10%. In molecular analyses of BRAF, the KIAA1549-BRAF (K16-B9) fusion gene was detected in all tumor regions, whereas BRAF V600E mutation was not detected by either conventional Sanger sequencing or the Eprobe-PCR method. Based on the results of the molecular analyses, this case was diagnosed as pilocytic astrocytoma.

Ganglioside synthase knock-out reduces prion disease incubation time in mouse models.
Kobayashi A, Qi Z, Shimazaki T, Munesue Y, Miyamoto T, Isoda N, Sawa H, Aoshima K, Kimura T, Mohri S, Kitamoto T, Yamashita T, Miyoshi I
The American journal of pathology, 189, 3, 677, 686, Dec. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid-containing glycosphingolipids (namely, gangliosides). Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft-associated proteins. To investigate the role of gangliosides in the pathogenesis of prion diseases, we performed intracerebral transmission study of a scrapie prion strain Chandler and a Gerstmann-Sträussler-Scheinker syndrome prion strain Fukuoka-1 using various knockout mouse strains ablated with ganglioside synthase gene (ie, GD2/GM2 synthase, GD3 synthase, or GM3 synthase). After challenge with the Chandler strain, GD2/GM2 synthase knockout mice showed 20% reduction of incubation time, reduced prion protein deposition in the brain with attenuated glial reactions, and reduced localization of prion proteins to lipid rafts. These results raise the possibility that the gangliosides may have an important role in prion disease pathogenesis by affecting the localization of prion proteins to lipid rafts.

Identification of group A rotaviruses from Zambian fruit bats provides evidence for long-distance dispersal events in Africa.
Sasaki M, Kajihara M, Changula K, Mori-Kajihara A, Ogawa H, Hang'ombe BM, Mweene AS, Simuunza M, Yoshida R, Carr M, Orba Y, Takada A, Sawa H
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 63, 104, 109, Sep. 2018, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Group A rotavirus (RVA) is a major cause of diarrhea in children worldwide. Although RVA infects many animals, little is known about RVA in bats. The present study investigated the genetic diversity of RVA in Zambian bats. We identified RVA from two straw-colored fruit bats (Eidolon helvum) and an Egyptian fruit bat (Rousettus aegyptiacus), and analyzed the genome sequences of these strains. Genome segments of the RVA strains from Zambian E. helvum showed 97%-99% nucleotide sequence identity with those of other RVA strains from E. helvum in Cameroon, which is 2800 km from the sampling locations. These findings suggest that migratory straw-colored fruit bat species, distributed across sub-Saharan Africa, have the potential to disseminate RVA across long distances. By contrast, the RVA strain from Zambian R. aegyptiacus carried highly divergent NSP2 and NSP4 genes, leading us to propose novel genotypes N21 and E27, respectively. Notably, this RVA strain also shared the same genotype for VP6 and NSP3 with the RVA strains from Zambian E. helvum, suggesting interspecies transmission and genetic reassortment may have occurred between these two bat species in the past. Our study has important implications for RVA dispersal in bat populations, and expands our knowledge of the ecology, diversity and evolutionary relationships of RVA.

チクングニアウイルスの増殖を制御する宿主因子の解析　　　　　　　　　　　　　　　
鳥居 志保, 和田 雄二, 佐々木 道仁, Hobson-Peters Jody, Hall Roy A., 大場 靖子, 澤 洋文
日本獣医学会学術集会講演要旨集, 161回, 345, 345, (公社)日本獣医学会, Aug. 2018
Japanese

First isolation of West Nile virus in Zambia from mosquitoes.
Orba Y, Hang'ombe BM, Mweene AS, Wada Y, Anindita PD, Phongphaew W, Qiu Y, Kajihara M, Mori-Kajihara A, Eto Y, Sasaki M, Hall WW, Eshita Y, Sawa H
Transboundary and emerging diseases, 65, 4, 933, 938, Aug. 2018, [Peer-reviewed], [Last author, Corresponding author]

Single amino acid mutation in dengue virus NS4B protein has opposing effects on viral proliferation in mammalian and mosquito cells.
Fujiki J, Nobori H, Sato A, Sasaki M, Carr M, Hall WW, Orba Y, Sawa H
Japanese journal of infectious diseases, 71, 6, 448, 454, Jul. 2018, [Peer-reviewed], [Last author, Corresponding author], [Domestic magazines]
English, Scientific journal, Dengue virus (DENV) has a considerable impact on the global health and is known to cause morbidity and mortality every year. By passaging DENV2 in baby hamster kidney (BHK)-21 cells, we isolated a mutant clone of DENV2 that shows rapid cytopathic effects in BHK-21 cells as compared with that showed by the parent strain. To investigate the relationship between amino acid mutations and proliferation activity of the isolated DENV2 clone, we performed full genome sequencing and identified 3 amino acid mutations in the coding region, the envelope T120K, NS4A M85T, and NS4B G124A. Genetically modified recombinant DENV2 (rDENV2) carrying the NS4A M85T and NS4B G124A mutations produced higher titers of progeny virus in BHK-21, Vero, and Huh-7 cells than in the wild-type (WT) rDENV2. rDENV2 with mutations at NS4A M85T and NS4B G124A failed to produce any plaques in C6/36 mosquito cell lines. Furthermore, rDENV2 possessing only the NS4B G124A mutation showed no plaque production in C6/36 cells but had higher viral titers in Vero and Huh-7 cells than the WT rDENV2 had. Our results clearly showed that the DENV2 NS4B G124A mutation has opposing effects on the virus proliferation in mosquito and certain mammalian cell lines.

Identification of Compound-B, a novel anti-dengue virus agent targeting the non-structural protein 4A.
Nobori H, Toba S, Yoshida R, Hall WW, Orba Y, Sawa H, Sato A
Antiviral research, 155, 60, 66, Jul. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever/dengue shock syndrome. At present, no antiviral drugs are available for treatment DENV infections. In this study, a screening system based on a DENV-infected cell-based assay identified a novel anti-DENV agent with a benzimidazole skeleton, named Compound-B, which demonstrated antiviral activity specific to four DENV serotypes (EC50: 1.32-4.12 μM). Analysis of a single amino acid substitution of Compound-B-resistant DENV2 revealed that mutation C87S in the non-structural protein 4A (NS4A) contributes to resistance to Compound-B.

The Unique Phylogenetic Position of a Novel Tick-Borne Phlebovirus Ensures an Ixodid Origin of the Genus Phlebovirus.
Keita Matsuno, Masahiro Kajihara, Ryo Nakao, Naganori Nao, Akina Mori-Kajihara, Mieko Muramatsu, Yongjin Qiu, Shiho Torii, Manabu Igarashi, Nodoka Kasajima, Keita Mizuma, Kentaro Yoshii, Hirofumi Sawa, Chihiro Sugimoto, Ayato Takada, Hideki Ebihara
mSphere, 3, 3, 27 Jun. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, The recent emergence of novel tick-borne RNA viruses has complicated the epidemiological landscape of tick-borne infectious diseases, posing a significant challenge to public health systems that seek to counteract tick-borne diseases. The identification of two novel tick-borne phleboviruses (TBPVs), severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV), as causative agents of severe illness in humans has accelerated the investigation and discoveries of novel TBPVs. In the present study, we isolated a novel TBPV designated Mukawa virus (MKWV) from host-questing Ixodes persulcatus females captured in Japan. Genetic characterization revealed that MKWV is a member of the genus Phlebovirus in the family Phenuiviridae Interestingly, MKWV is genetically distinct from other known TBPVs and shares a most recent common ancestor with mosquito/sandfly-borne (insect-borne) phleboviruses. Despite its genetic similarity to insect-borne phleboviruses, the molecular footprints of its viral proteins and its biological characteristics define MKWV as a tick-borne virus that can be transmitted to mammals. A phylogenetic ancestral-state reconstruction for arthropod vectors of phleboviruses including MKWV based on viral L segment sequences indicated that ticks likely harbored ancestral phleboviruses that evolved into both the tick-borne and MKWV/insect-borne phlebovirus lineages. Overall, our findings suggest that most of the phlebovirus evolution has occurred in hard ticks to generate divergent viruses, which may provide a seminal foundation for understanding the mechanisms underlying the evolution and emergence of pathogenic phleboviruses, such as Rift Valley fever virus and SFTSV/HRTV.IMPORTANCE The emergence of novel tick-borne RNA viruses causing severe illness in humans has complicated the epidemiological landscape of tick-borne diseases, requiring further investigation to safeguard public health. In the present study, we discovered a novel tick-borne phlebovirus from Ixodes persulcatus ticks in Japan. While its viral RNA genome sequences were similar to those of mosquito/sandfly-borne viruses, molecular and biological footprints confirmed that this is a tick-borne virus. The unique evolutionary position of the virus allowed us to estimate the ancestral phlebovirus vector, which was likely a hard tick. Our findings may provide a better understanding of the evolution and emergence of phleboviruses associated with emerging infectious diseases, such as severe fever with thrombocytopenia syndrome (SFTS) and Heartland virus disease.

Ribavirin-related compounds exert in vitro inhibitory effects toward rabies virus.
Anindita PD, Sasaki M, Okada K, Ito N, Sugiyama M, Saito-Tarashima N, Minakawa N, Shuto S, Otsuguro S, Ichikawa S, Matsuda A, Maenaka K, Orba Y, Sawa H
Antiviral research, 154, 1, 9, Jun. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Rabies remains an invariably fatal neurological disease despite the availability of a preventive vaccination and post-exposure prophylaxis that must be immediately administered to the exposed individual before symptom onset. There is no effective medication for treatment during the symptomatic phase. Ribavirin, a guanine nucleoside analog, is a potent inhibitor of rabies virus (RABV) replication in vitro but lacks clinical efficacy. Therefore, we attempted to identify potential ribavirin analogs with comparable or superior anti-RABV activity. Antiviral activity and cytotoxicity of the compounds were initially examined in human neuroblastoma cells. Among the tested compounds, two exhibited a 5- to 27-fold higher anti-RABV activity than ribavirin. Examination of the anti-RABV mechanisms of action of the compounds using time-of-addition and minigenome assays revealed that they inhibited viral genome replication and transcription. Addition of exogenous guanosine to RABV-infected cells diminished the antiviral activity of the compounds, suggesting that they are involved in guanosine triphosphate (GTP) pool depletion by inhibiting inosine monophosphate dehydrogenase (IMPDH). Taken together, our findings underline the potency of nucleoside analogs as a class of antiviral compounds for the development of novel agents against RABV.

Tick-borne haemoparasites and Anaplasmataceae in domestic dogs in Zambia.
Qiu Y, Kaneko C, Kajihara M, Ngonda S, Simulundu E, Muleya W, Thu MJ, Hang'ombe MB, Katakura K, Takada A, Sawa H, Simuunza M, Nakao R
Ticks and tick-borne diseases, 9, 4, 988, 995, Elsevier BV, May 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Tick-borne diseases (TBDs), including emerging and re-emerging infectious diseases, are important threats to human and animal health worldwide. Indeed, the number of reported human and animal infectious cases of novel TBD agents has increased in recent decades. However, TBDs tend to be neglected, especially in resource-limited countries that often have limited diagnostic capacity. The aim of this molecular survey was to detect and characterise tick-borne pathogens (Babesia, Theileria, and Hepatozoon parasites and Anaplasmataceae bacteria) in domestic dogs in Zambia. In total, 247 canine peripheral blood samples were collected in Lusaka, Mazabuka, Monze, and Shangombo. Conventional PCR to detect the selected pathogens was performed using DNA extracted from canine blood. One hundred eleven samples were positive for protozoa and 5 were positive for Anaplasmataceae. Sequencing of thirty-five randomly selected protozoa-positive samples revealed the presence of Babesia rossi, Babesia vogeli, and Hepatozoon canis 18S rDNA. Based on these sequences, a multiplex PCR system was developed to yield PCR products with different amplicons, the size of which depended on the parasite species; thus, each species could be identified without the need for sequence analysis. Approximately 40% of dogs were positive for H. canis. In particular, the positive rate (75.2%) of H. canis infection was significantly higher in Shangombo than in other sampling sites. Multiplex PCR assay detected B. rossi and B. vogeli infections in five and seven dogs, respectively, indicating that this approach is useful for detecting parasites with low prevalence. Sequencing analysis of gltA and groEL genes of Anaplasmataceae revealed that two and one dogs in Lusaka were infected with Anaplasma platys and Ehrlichia canis, respectively. The data indicated that Zambian dogs were infected with multiple tick-borne pathogens such as H. canis, B. rossi, B. vogeli, A. platys, E. canis and uncharacterized Ehrlichia sp. Since some of these parasites are zoonotic, concerted efforts are needed to raise awareness of, and control, these tick-borne pathogens.

The Role of Heparan Sulfate Proteoglycans as an Attachment Factor for Rabies Virus Entry and Infection.
Sasaki M, Anindita PD, Ito N, Sugiyama M, Carr M, Fukuhara H, Ose T, Maenaka K, Takada A, Hall WW, Orba Y, Sawa H
The Journal of infectious diseases, 217, 11, 1740, 1749, May 2018, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Rabies virus (RABV) is the causative agent of fatal neurological disease. Cellular attachment is the initial and essential step for viral infections. Although extensive studies have demonstrated that RABV uses various target cell molecules to mediate infection, no specific molecule has been identified as an attachment factor for RABV infection. Here we demonstrate that cellular heparan sulfate (HS) supports RABV adhesion and subsequent entry into target cells. Enzymatic removal of HS reduced cellular susceptibility to RABV infection, and heparin, a highly sulfated form of HS, blocked viral adhesion and infection. The direct binding between RABV glycoprotein and heparin was demonstrated, and this interaction was shown to require HS N- and 6-O-sulfation. We also revealed that basic amino acids in the ectodomain of RABV glycoprotein serve as major determinants for the RABV-HS interaction. Collectively, our study highlights a previously undescribed role of HS as an attachment factor for RABV infection.

Discovery of Mwinilunga alphavirus: A novel alphavirus in Culex mosquitoes in Zambia.
Torii S, Orba Y, Hang'ombe BM, Mweene AS, Wada Y, Anindita PD, Phongphaew W, Qiu Y, Kajihara M, Mori-Kajihara A, Eto Y, Harima H, Sasaki M, Carr M, Hall WW, Eshita Y, Abe T, Sawa H
Virus research, 250, 31, 36, May 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Mosquito-borne alphaviruses are disseminated globally and cause febrile illness in humans and animals. Since the prevalence and diversity of alphaviruses has not been previously investigated in Zambia, reverse transcription PCR was employed as a broad-spectrum approach for the detection of alphaviruses in mosquitoes. From 552 mosquito pools, a novel alphavirus, tentatively named Mwinilunga alphavirus (MWAV), was discovered from a single Culex quinquefasciatus mosquito pool. The full genome of MWAV was subsequently determined, and pairwise comparisons demonstrated that MWAV represented a new alphavirus species. Phylogenetic analyses and a linear discriminant analysis based on the dinucleotide ratios in various virus sequences indicated that MWAV is related to a mosquito-specific alphavirus distinct from other known mosquito-borne alphaviruses due to its inability to replicate in vertebrate cell lines. Further analyses of these novel alphaviruses will help to facilitate a greater understanding of the molecular determinants of host range restriction and the evolutionary relationships of alphaviruses.

Detection of novel gammaherpesviruses from fruit bats in Indonesia.
Wada Y, Sasaki M, Setiyono A, Handharyani E, Rahmadani I, Taha S, Adiani S, Latief M, Kholilullah ZA, Subangkit M, Kobayashi S, Nakamura I, Kimura T, Orba Y, Sawa H
Journal of medical microbiology, 67, 3, 415, 422, Microbiology Society, Mar. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Bats are an important natural reservoir of zoonotic viral pathogens. We previously isolated an alphaherpesvirus in fruit bats in Indonesia, and here establish the presence of viruses belonging to other taxa of the family Herpesviridae. We screened the same fruit bat population with pan-herpesvirus PCR and discovered 68 sequences of novel gammaherpesvirus, designated 'megabat gammaherpesvirus' (MgGHV). A phylogenetic analysis of approximately 3.4 kbp of continuous MgGHV sequences encompassing the glycoprotein B gene and DNA polymerase gene revealed that the MgGHV sequences are distinct from those of other reported gammaherpesviruses. Further analysis suggested the existence of co-infections of herpesviruses in Indonesian fruit bats. Our findings extend our understanding of the infectious cycles of herpesviruses in bats in Indonesia and the phylogenetic diversity of the gammaherpesviruses.

Shape-dependent adjuvanticity of nanoparticle-conjugated RNA adjuvants for intranasal inactivated influenza vaccines
Tazaki Taiyu, Tabata Koshiro, Ainai Akira, Ohara Yuki, Kobayashi Shintaro, Ninomiya Takafumi, Orba Yasuko, Mitomo Hideyuki, Nakano Tetsuo, Hasegawa Hideki, Ijiro Kuniharu, Sawa Hirofumi, Suzuki Tadaki, Niikura Kenichi
RSC ADVANCES, 8, 30, 16527, 16536, 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal

Development of a quick bioassay for the evaluation of transmission properties of acquired prion diseases.
Munesue Y, Shimazaki T, Qi Z, Isoda N, Sawa H, Aoshima K, Kimura T, Mohri S, Kitamoto T, Kobayashi A
Neuroscience letters, 668, 43, 47, Elsevier BV, Jan. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Evaluation of transmission properties is important for the differential diagnosis of a subgroup of acquired Creutzfeldt-Jakob disease (CJD) with methionine homozygosity at polymorphic codon 129 of the PRNP gene, an intermediate type abnormal prion protein (PrP), and kuru plaques, denoted as acquired CJD-MMiK. The present study aimed to develop a quick evaluation system of the transmission properties of acquired CJD-MMiK. In the PrP-humanized mice intraperitoneally inoculated with brain homogenates from an acquired CJD-MMiK patient, accumulation of abnormal PrP was observed in follicular dendritic cells of the spleen at 75 days post-inoculation. The transmission properties of acquired CJD-MMiK were quite different from those of sporadic CJD with the same PRNP codon 129 genotype. Moreover, even at 14 days post-inoculation, the characteristic transmission properties of acquired CJD-MMiK could be detected. These findings suggest that the bioassay using follicular dendritic cells of the spleen, named as a FDC assay, can be an easy, time-saving, and useful method to distinguish acquired CJD-MMiK from sporadic CJD.

Development of a rapid and quantitative method for the analysis of viral entry and release using a NanoLuc luciferase complementation assay
Michihito Sasaki, Paulina D. Anindita, Wallaya Phongphaew, Michael Carr, Shintaro Kobayashi, Yasuko Orba, Hirofumi Sawa
VIRUS RESEARCH, 243, 69, 74, Jan. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal

Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat (Eidolon helvum).
Hirohito Ogawa, Masahiro Kajihara, Naganori Nao, Asako Shigeno, Daisuke Fujikura, Bernard M Hang'ombe, Aaron S Mweene, Alisheke Mutemwa, David Squarre, Masao Yamada, Hideaki Higashi, Hirofumi Sawa, Ayato Takada
Viruses, 9, 12, 04 Dec. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal, Bats are important reservoirs for emerging zoonotic viruses. For extensive surveys of potential pathogens in straw-colored fruit bats (Eidolon helvum) in Zambia, a total of 107 spleen samples of E. helvum in 2006 were inoculated onto Vero E6 cells. The cell culture inoculated with one of the samples (ZFB06-106) exhibited remarkable cytopathic changes. Based on the ultrastructural property in negative staining and cross-reactivity in immunofluorescence assays, the virus was suspected to be an adenovirus, and tentatively named E. helvum adenovirus 06-106 (EhAdV 06-106). Analysis of the full-length genome of 30,134 bp, determined by next-generation sequencing, showed the presence of 28 open reading frames. Phylogenetic analyses confirmed that EhAdV 06-106 represented a novel bat adenovirus species in the genus Mastadenovirus. The virus shared similar characteristics of low G + C contents with recently isolated members of species Bat mastadenoviruses E, F and G, from which EhAdV 06-106 diverged by more than 15% based on the distance matrix analysis of DNA polymerase amino acid sequences. According to the taxonomic criteria, we propose the tentative new species name "Bat mastadenovirus H". Because EhAdV 06-106 exhibited a wide in vitro cell tropism, the virus might have a potential risk as an emerging virus through cross-species transmission.

発光タグHiBiTを使用したフラビウイルスの細胞内侵入および出芽機構の解析　　　　　　　　　　　　　　　
佐々木 道仁, アニンディタ・パウリナ, ポンペオウ・ワンラヤー, カー・マイケル, 小林 進太郎, 大場 靖子, 澤 洋文
生命科学系学会合同年次大会, 2017年度, [1P, 1118], 生命科学系学会合同年次大会運営事務局, Dec. 2017
Japanese

Identification of the same polyomavirus species in different African horseshoe bat species is indicative of short-range host-switching events
Michael Carr, Gabriel Gonzalez, Michihito Sasaki, Serena E. Dool, Kimihito Ito, Akihiro Ishii, Bernard M. Hang'ombe, Aaron S. Mweene, Emma C. Teeling, William W. Hall, Yasuko Orba, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 98, 11, 2771, 2785, Nov. 2017, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

チクングニアウイルスのRNA依存性RNAポリメラーゼを阻害する新規抗ウイルス化合物の探索と解析　　　　　　　　　　　　　　　
和田 雄治, 大場 靖子, 佐々木 道仁, 小林 進太郎, Carr Michael, 登 治謙, 佐藤 彰彦, Hall William, 澤 洋文
日本獣医学会学術集会講演要旨集, 160回, 391, 391, (公社)日本獣医学会, Aug. 2017
Japanese

Discovery of novel cyclic peptide inhibitors of dengue virus NS2B-NS3 protease with antiviral activity
Youhei Takagi, Kouhei Matsui, Haruaki Nobori, Haruka Maeda, Akihiko Sato, Takeshi Kurosu, Yasuko Orba, Hirofumi Sawa, Kazunari Hattori, Kenichi Higashino, Yoshito Numata, Yutaka Yoshida
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 27, 15, 3586, 3590, Aug. 2017, [Peer-reviewed]
English, Scientific journal

2016 International meeting of the Global Virus Network
Ramesh Akkina, Heinz Ellerbrok, William Hall, Hideki Hasegawa, Yasushi Kawaguchi, Harold Kleanthous, Edward McSweegan, Natalia Mercer, Victor Romanowski, Hirofumi Sawa, Anders Vahlne
ANTIVIRAL RESEARCH, 142, 21, 29, Jun. 2017, [Peer-reviewed]
English, Scientific journal

Listeria monocytogenes serotype 4b strains replicate in monocytes/macrophages more than the other serotypes
Rie Hasebe, Ryo Nakao, Aiko Ohnuma, Takeshi Yamasaki, Hirofumi Sawa, Shinji Takai, Motohiro Horiuchi
JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 6, 962, 969, Jun. 2017, [Peer-reviewed]
English, Scientific journal

Discovery of a novel antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus
Yuji Wada, Yasuko Orba, Michihito Sasaki, Shintaro Kobayashi, Michael J. Carr, Haruaki Nobori, Akihiko Sato, William W. Hall, Hirofumi Sawa
VIROLOGY, 505, 102, 112, May 2017, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Discovery of African bat polyomaviruses and infrequent recombination in the large T antigen in the Polyomaviridae
Michael Carr, Gabriel Gonzalez, Michihito Sasaki, Kimihito Ito, Akihiro Ishii, Bernard M. Hang'ombe, Aaron S. Mweene, Yasuko Orba, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 98, 4, 726, 738, Apr. 2017, [Peer-reviewed]
English, Scientific journal

Isolation of a simian immunodeficiency virus from a malbrouck (Chlorocebus cynosuros)
Michael Carr, Akira Kawaguchi, Michihito Sasaki, Gabriel Gonzalez, Kimihito Ito, Yuka Thomas, Bernard M. Hang'ombe, Aaron S. Mweene, Guoyan Zhao, David Wang, Yasuko Orba, Akihiro Ishii, Hirofumi Sawa
ARCHIVES OF VIROLOGY, 162, 2, 543, 548, Feb. 2017, [Peer-reviewed]
English, Scientific journal

Putative RNA viral sequences detected in an Ixodes scapularis-derived cell line
Ryo Nakao, Keita Matsuno, Yongjin Qiu, Junki Marilyama, Nao Eguchi, Naganori Nao, Masahiro Kajihara, Kentaro Yoshii, Hirofumi Sawa, Ayato Takada, Chihiro Sugimoto
TICKS AND TICK-BORNE DISEASES, 8, 1, 103, 111, 2017, [Peer-reviewed]
English, Scientific journal

Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus
Wallaya Phongphaew, Shintaro Kobayashi, Michihito Sasaki, Michael Carr, William W. Hall, Yasuko Orba, Hirofumi Sawa
VIRUS RESEARCH, 228, 114, 123, Jan. 2017, [Peer-reviewed]
English, Scientific journal

An optimistic protein assembly from sequence reads salvaged an uncharacterized segment of mouse picobirnavirus
Gabriel Gonzalez, Michihito Sasaki, Lucy Burkitt-Gray, Tomonori Kamiya, Noriko M. Tsuji, Hirofumi Sawa, Kimihito Ito
SCIENTIFIC REPORTS, 7, 40447, Jan. 2017, [Peer-reviewed]
English, Scientific journal

Multi-reassortant G3P[3] group A rotavirus in a horseshoe bat in Zambia
Michihito Sasaki, Yasuko Orba, Satoko Sasaki, Gabriel Gonzalez, Akihiro Ishii, Bernard M. Hang'ombe, Aaron S. Mweene, Kimihito Ito, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 97, 10, 2488, 2493, Oct. 2016, [Peer-reviewed]
English, Scientific journal

Generation of recombinant rabies viruses encoding NanoLuc luciferase for antiviral activity assays
Paulina Duhita Anindita, Michihito Sasaki, Haruaki Nobori, Akihiko Sato, Michael Carr, Naoto Ito, Makoto Sugiyama, Yasuko Orba, Hirofumi Sawa
VIRUS RESEARCH, 215, 121, 128, Apr. 2016, [Peer-reviewed]
English, Scientific journal

Divergent bufavirus harboured in megabats represents a new lineage of parvoviruses
Michihito Sasaki, Gabriel Gonzalez, Yuji Wada, Agus Setiyono, Ekowati Handharyani, Ibenu Rahmadani, Siswatiana Taha, Sri Adiani, Munira Latief, Zainal Abidin Kholilullah, Mawar Subangkit, Shintaro Kobayashi, Ichiro Nakamura, Takashi Kimura, Yasuko Orba, Kimihito Ito, Hirofumi Sawa
SCIENTIFIC REPORTS, 6, 24257, Apr. 2016, [Peer-reviewed]
English, Scientific journal

Rab8b Regulates Transport of West Nile Virus Particles from Recycling Endosomes
Shintaro Kobayashi, Tadaki Suzuki, Akira Kawaguchi, Wallaya Phongphaew, Kentaro Yoshii, Tomohiko Iwano, Akihiro Harada, Hiroaki Kariwa, Yasuko Orba, Hirofumi Sawa
JOURNAL OF BIOLOGICAL CHEMISTRY, 291, 12, 6559, 6568, Mar. 2016, [Peer-reviewed]
English, Scientific journal

チクングニアウイルスの増殖を抑制する新規化合物の探索及び作用機序の解明に向けた基礎研究　　　　　　　　　　　　　　　
和田 雄治, 大場 靖子, 佐々木 道仁, 登 治謙, 佐藤 彰彦, 澤 洋文
日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1P1143], [1P1143], (公社)日本生化学会, Dec. 2015
English

Seroepidemiological Prevalence of Multiple Species of Filoviruses in Fruit Bats (Eidolon helvum) Migrating in Africa
Hirohito Ogawa, Hiroko Miyamoto, Eri Nakayama, Reiko Yoshida, Ichiro Nakamura, Hirofumi Sawa, Akihiro Ishii, Yuka Thomas, Emiko Nakagawa, Keita Matsuno, Masahiro Kajihara, Junki Maruyama, Naganori Nao, Mieko Muramatsu, Makoto Kuroda, Edgar Simulundu, Katendi Changula, Bernard Hang'ombe, Boniface Namangala, Andrew Nambota, Jackson Katampi, Manabu Igarashi, Kimihito Ito, Heinz Feldmann, Chihiro Sugimoto, Ladslav Moonga, Aaron Mweene, Ayato Takada
JOURNAL OF INFECTIOUS DISEASES, 212, S101, S108, Oct. 2015, [Peer-reviewed]
English, Scientific journal

野生動物から検出された新規パルボウイルスの系統解析　　　　　　　　　　　　　　　
佐々木 道仁, 大場 靖子, Anindita D. Paulina, 石井 秋宏, 伊藤 公人, 澤 洋文
日本獣医学会学術集会講演要旨集, 158回, 340, 340, (公社)日本獣医学会, Aug. 2015
Japanese

Distinct Lineages of Bufavirus in Wild Shrews and Nonhuman Primates
Michihito Sasaki, Yasuko Orba, Paulina D. Anindita, Akihiro Ishii, Keisuke Ueno, Bernard M. Hang'ombe, Aaron S. Mweeile, Kimihito Ito, Hirofumi Sawa
EMERGING INFECTIOUS DISEASES, 21, 7, 1230, 1233, Jul. 2015, [Peer-reviewed]
English, Scientific journal

Tyr724 phosphorylation of ELMO1 by Src is involved in cell spreading and migration via Rac1 activation
Yoshinori Makino, Masumi Tsuda, Yusuke Ohba, Hiroshi Nishihara, Hirofumi Sawa, Kazuo Nagashima, Shinya Tanaka
CELL COMMUNICATION AND SIGNALING, 13, 35, Jul. 2015, [Peer-reviewed]
English, Scientific journal

Paternal H3K4 methylation is required for minor zygotic gene activation and early mouse embryonic development
Keisuke Aoshima, Erina Inoue, Hirofumi Sawa, Yuki Okada
EMBO REPORTS, 16, 7, 803, 812, Jul. 2015, [Peer-reviewed]
English, Scientific journal

Molecular epidemiology of pathogenic Leptospira spp. in the straw-colored fruit bat (Eidolon helvum) migrating to Zambia from the Democratic Republic of Congo
Hirohito Ogawa, Nobuo Koizumi, Aiko Ohnuma, Alisheke Mutemwa, Bernard M. Hang'ombe, Aaron S. Mweene, Ayato Takada, Chihiro Sugimoto, Yasuhiko Suzuki, Hiroshi Kida, Hirofumi Sawa
INFECTION GENETICS AND EVOLUTION, 32, 143, 147, Jun. 2015, [Peer-reviewed]
English, Scientific journal

Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.
Kesdangsakonwut S, Sunden Y, Yamada K, Nishizono A, Sawa H, Umemura T
Veterinary pathology, 52, 3, 573, 575, May 2015, [Peer-reviewed]

Detection of coronavirus genomes in Moluccan naked-backed fruit bats in Indonesia
Paulina Duhita Anindita, Michihito Sasaki, Agus Setiyono, Ekowati Handharyani, Yasuko Orba, Shintaro Kobayashi, Ibnu Rahmadani, Siswatiana Taha, Sri Adiani, Mawar Subangkit, Ichiro Nakamura, Hirofumi Sawa, Takashi Kimura
ARCHIVES OF VIROLOGY, 160, 4, 1113, 1118, Apr. 2015, [Peer-reviewed]
English, Scientific journal

Detection of novel polyomaviruses in fruit bats in Indonesia
Shintaro Kobayashi, Michihito Sasaki, Ryo Nakao, Agus Setiyono, Ekowati Handharyani, Yasuko Orba, Ibnu Rahmadani, Siswatiana Taha, Sri Adiani, Mawar Subangkit, Ichiro Nakamura, Takashi Kimura, Hirofumi Sawa
ARCHIVES OF VIROLOGY, 160, 4, 1075, 1082, Apr. 2015, [Peer-reviewed]
English, Scientific journal

Orthopoxvirus infection among wildlife in Zambia
Yasuko Orba, Michihito Sasaki, Hiroki Yamaguchi, Akihiro Ishii, Yuka Thomas, Hirohito Ogawa, Bernard M. Hang'ombe, Aaron S. Mweene, Shigeru Morikawa, Masayuki Saijo, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 96, Pt 2, 390, 394, Feb. 2015, [Peer-reviewed]
English, Scientific journal

Metagenomic analysis of the shrew enteric virome reveals novel viruses related to human stool-associated viruses
Michihito Sasaki, Yasuko Orba, Keisuke Ueno, Akihiro Ishii, Ladslav Moonga, Bernard M. Hang'ombe, Aaron S. Mweene, Kimihito Ito, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 96, Pt 2, 440, 452, Feb. 2015, [Peer-reviewed]
English, Scientific journal

Pathological and molecular diagnosis of the 2013 African swine fever outbreak in Lusaka, Zambia
John Yabe, Pharaoh Hamambulu, Edgar Simulundu, Hirohito Ogawa, Masahiro Kajihara, Akina Mori-Kajihara, Katendi Changula-Chitanga, Max Mwase, Mutinta Mweemba-Muwowo, Herman Moses Chambaro, Liywalii Mataa, Bernard Hang'ombe, Bonniface Namangala, Paul Fandamu, Hirofumi Sawa, Ayato Takada, Hideaki Higashi, Aaron Simanyengwe Mweene
TROPICAL ANIMAL HEALTH AND PRODUCTION, 47, 2, 459, 463, Feb. 2015, [Peer-reviewed]
English, Scientific journal

A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice
Akihiro Ishii, Keisuke Ueno, Yasuko Orba, Michihito Sasaki, Ladslav Moonga, Bernard M. Hang'ombe, Aaron S. Mweene, Takashi Umemura, Kimihito Ito, William W. Hall, Hirofumi Sawa
NATURE COMMUNICATIONS, 5, 5651, Dec. 2014, [Peer-reviewed]
English, Scientific journal

The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia
Edgar Simulundu, Naganori Nao, John Yabe, Nilton A. Muto, Thami Sithebe, Hirofumi Sawa, Rashid Manzoor, Masahiro Kajihara, Mieko Muramatsu, Akihiro Ishii, Hirohito Ogawa, Aaron S. Mweene, Ayato Takada
ARCHIVES OF VIROLOGY, 159, 10, 2633, 2640, Oct. 2014, [Peer-reviewed]
English, Scientific journal

Autophagy inhibits viral genome replication and gene expression stages in West Nile virus infection
Shintaro Kobayashi, Yasuko Orba, Hiroki Yamaguchi, Kenta Takahashi, Michihito Sasaki, Rie Hasebe, Takashi Kimura, Hirofumi Sawa
VIRUS RESEARCH, 191, 83, 91, Oct. 2014, [Peer-reviewed]
English, Scientific journal

Detection and characterization of zoonotic pathogens of free-ranging non-human primates from Zambia
Jesca Nakayima, Kyoko Hayashida, Ryo Nakao, Akihiro Ishii, Hirohito Ogawa, Ichiro Nakamura, Ladslav Moonga, Bernard M. Hang'ombe, Aaron S. Mweene, Yuka Thomas, Yasuko Orba, Hirofumi Sawa, Chihiro Sugimoto
PARASITES & VECTORS, 7, 490, Oct. 2014, [Peer-reviewed]
English, Scientific journal

Isolation and Characterization of a Novel Alphaherpesvirus in Fruit Bats
Michihito Sasaki, Agus Setiyono, Ekowati Handharyani, Shintaro Kobayashi, Ibenu Rahmadani, Siswatiana Taha, Sri Adiani, Mawar Subangkit, Ichiro Nakamura, Hirofumi Sawa, Takashi Kimura
JOURNAL OF VIROLOGY, 88, 17, 9819, 9829, Sep. 2014, [Peer-reviewed]
English, Scientific journal

Survival of rabid rabbits after intrathecal immunization
Sawang Kesdangsakonwut, Yuji Sunden, Keisuke Aoshima, Yoshimi Iwaki, Masahiro Okumura, Hirofumi Sawa, Takashi Umemura
NEUROPATHOLOGY, 34, 3, 277, 283, Jun. 2014, [Peer-reviewed]
English, Scientific journal

Role of the C-Terminal Region of Vervet Monkey Polyomavirus 1 VP1 in Virion Formation
Hiroki Yamaguchi, Shintaro Kobayashi, Junki Maruyama, Michihito Sasaki, Ayato Takada, Takashi Kimura, Hirofumi Sawa, Yasuko Orba
JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 5, 637, 644, May 2014, [Peer-reviewed]
English, Scientific journal

Molecular Epidemiology of Paramyxoviruses in Frugivorous Eidolon helvum Bats in Zambia
Walter Muleya, Michihito Sasaki, Yasuko Orba, Akihiro Ishii, Yuka Thomas, Emiko Nakagawa, Hirohito Ogawa, Bernard Hang'ombe, Boniface Namangala, Aaron Mweene, Ayato Takada, Takashi Kimura, Hirofumi Sawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 76, 4, 611, 614, Apr. 2014, [Peer-reviewed]
English, Scientific journal

Molecular epidemiology of paramyxoviruses in Zambian wild rodents and shrews
Michihito Sasaki, Walter Muleya, Akihiro Ishii, Yasuko Orba, Bernard M. Hang'ombe, Aaron S. Mweene, Ladslav Moonga, Yuka Thomas, Takashi Kimura, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 95, Pt 2, 325, 330, Feb. 2014, [Peer-reviewed]
English, Scientific journal

Establishment of tracking system for West Nile virus entry and evidence of microtubule involvement in particle transport
Yoshinori Makino, Tadaki Suzuki, Rie Hasebe, Takashi Kimura, Akihiko Maeda, Hidehiro Takahashi, Hirofumi Sawa
JOURNAL OF VIROLOGICAL METHODS, 195, 250, 257, Jan. 2014, [Peer-reviewed]
English, Scientific journal

A novel HSP90 inhibitor, 17-DMAG, induces Tax down-regulation and its oral administration to ATL-model mice intervenes against the infiltration property of the ATL-like lymphocytes and provides extended survival period
Emi Ikebe, Akira Kawaguchi, Kenta Tezuka, Shinya Taguchi, Satoshi Hirose, Takashi Matsumoto, Takahiro Mitsui, Kazuyo Senba, Akira Nishizono, Mitsuo Hori, Hiroo Hasegawa, Yasuaki Yamada, Takaharu Ueno, Yuetsu Tanaka, Hirofumi Sawa, William Hall, Yasuaki Minami, Kuan-Teh Jeang, Masao Ogata, Kazuhiro Morishita, Hideki Hasegawa, Jun-ichi Fujisawa, Hidekatsu Iha
Retrovirology, 11(Suppl 1), P44, 2014, [Peer-reviewed]

Surveillance and diagnosis of plague and anthrax in Tanzania and Zambia
B. M. Hang’ombe, M. Ziwa, M. Haule, I. Nakamura, K. L. Samui, D. Kaile, A. S. Mweene, B. S. Kilonzo, E. F. Lyamuya, M. Matee, C. Sugimoto, H. Sawa, B. W. Wren
Onderstepoort Journal of Veterinary Research, 81, 2, Agricultural Research Council, 2014, [Peer-reviewed]
English, Scientific journal

[Epidemiological and basic research activity targeting polyomaviruses].
Sawa H, Kobayashi S, Suzuki T, Orba Y
Uirusu, 64, 1, 25, 34, 2014, [Peer-reviewed]

Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3
Tadaki Suzuki, Yasuko Orba, Yoshinori Makino, Yuki Okada, Yuji Sunden, Hideki Hasegawa, William W. Hall, Hirofumi Sawa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110, 46, 18668, 18673, Nov. 2013, [Peer-reviewed]
English, Scientific journal

Cysteine Residues in the Major Capsid Protein, Vp1, of the JC Virus Are Important for Protein Stability and Oligomer Formation
Shintaro Kobayashi, Tadaki Suzuki, Manabu Igarashi, Yasuko Orba, Noriko Ohtake, Keita Nagakawa, Kenichi Niikura, Takashi Kimura, Harumi Kasamatsu, Hirofumi Sawa
PLoS ONE, 8, 10, e76668, 10, 09 Oct. 2013, [Peer-reviewed]
English, Scientific journal

Characterization of Japanese encephalitis virus infection in an immortalized mesencephalic cell line, CSM14.1
Takashi Kimura, Megumi Okumura, Eunmi Kim, Michihito Sasaki, Yasuko Orba, Hirofumi Sawa
MICROBIOLOGY AND IMMUNOLOGY, 57, 10, 723, 731, Oct. 2013, [Peer-reviewed]
English, Scientific journal

Human Parainfluenza Virus Type 3 in Wild Nonhuman Primates, Zambia
Michihito Sasaki, Akihiro Ishii, Yasuko Orba, Yuka Thomas, Bernard M. Hang'ombe, Ladslav Moonga, Aaron S. Mweene, Hirohito Ogawa, Ichiro Nakamura, Takashi Kimura, Hirofumi Sawa
EMERGING INFECTIOUS DISEASES, 19, 9, 1500, 1503, Sep. 2013, [Peer-reviewed]
English, Scientific journal

De novo sequence analysis of cytochrome P450 1-3 genes expressed in ostrich liver with highest expression of CYP2G19
Yusuke K. Kawai, Kensuke P. Watanabe, Akihiro Ishii, Aiko Ohnuma, Hirofumi Sawa, Yoshinori Ikenaka, Mayumi Ishizuka
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS, 8, 3, 201, 208, Sep. 2013, [Peer-reviewed]
English, Scientific journal

Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice
E. Ikebe, A. Kawaguchi, K. Tezuka, S. Taguchi, S. Hirose, T. Matsumoto, T. Mitsui, K. Senba, A. Nishizono, M. Hori, H. Hasegawa, Y. Yamada, T. Ueno, Y. Tanaka, H. Sawa, W. Hall, Y. Minami, K. T. Jeang, M. Ogata, K. Morishita, H. Hasegawa, J. Fujisawa, H. Iha
Blood Cancer Journal, 3, 8, e132, Aug. 2013, [Peer-reviewed]
English, Scientific journal

ラット中脳由来神経細胞株CSM14.1における日本脳炎ウイルス感染様式　　　　　　　　　　　　　　　
木村 享史, 奥村 恵, 金 恩美, 佐々木 道仁, 大場 靖子, 澤 洋文
日本獣医学会学術集会講演要旨集, 156回, 214, 214, (公社)日本獣医学会, Aug. 2013
Japanese

オートファジーによるウエストナイルウイルス増殖抑制機構の解明　　　　　　　　　　　　　　　
小林 進太郎, 大場 靖子, 山口 宏樹, 佐々木 道仁, 長谷部 理絵, 木村 享史, 澤 洋文
日本獣医学会学術集会講演要旨集, 156回, 267, 267, (公社)日本獣医学会, Aug. 2013
Japanese

インドネシア共和国に生息するオオコウモリから分離した新規ヘルペスウイルスの性状解析　　　　　　　　　　　　　　　
佐々木 道仁, Agus Setiyono, Ekowati Handharyani, 中村 一郎, 澤 洋文, 木村 享史
日本獣医学会学術集会講演要旨集, 156回, 283, 283, (公社)日本獣医学会, Aug. 2013
Japanese

Cross-Reactivity of Secondary Antibodies against African Rodents and Application for Sero-Surveillance
Ichiro Nakamura, Bernard Mudenda Hang'ombe, Hirofumi Sawa, Shintaro Kobayashi, Yasuko Orba, Akihiro Ishii, Yuka Thomas, Rie Isozumi, Kumiko Yoshimatsu, Aaron S. Mweene, Ayato Takada, Chihiro Sugimoto, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 6, 819, 825, Jun. 2013, [Peer-reviewed]
English, Scientific journal

Identification of a novel polyomavirus from vervet monkeys in Zambia
Hiroki Yamaguchi, Shintaro Kobayashi, Akihiro Ishii, Hirohito Ogawa, Ichiro Nakamura, Ladslav Moonga, Bernard M. Hang'ombe, Aaron S. Mweene, Yuka Thomas, Takashi Kimura, Hirofumi Sawa, Yasuko Orba
Journal of General Virology, 94, 6, 1357, 1364, Pt 6, 01 Jun. 2013, [Peer-reviewed]
English, Scientific journal

Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo
Kenichi Niikura, Tatsuya Matsunaga, Tadaki Suzuki, Shintaro Kobayashi, Hiroki Yamaguchi, Yasuko Orba, Akira Kawaguchi, Hideki Hasegawa, Kiichi Kajino, Takafumi Ninomiya, Kuniharu Ijiro, Hirofumi Sawa
ACS NANO, 7, 5, 3926, 3938, May 2013, [Peer-reviewed]
English, Scientific journal

Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells
Kenichi Niikura, Naotoshi Sugimura, Yusuke Musashi, Shintaro Mikuni, Yasutaka Matsuo, Shintaro Kobayashi, Keita Nagakawa, Shuko Takahara, Chie Takeuchi, Hirofumi Sawa, Masataka Kinjo, Kuniharu Ijiro
Molecular BioSystems, 9, 3, 501, 507, 3, Mar. 2013, [Peer-reviewed]
English, Scientific journal

Relationship between Methyl CpG Binding Protein 2 and JC Viral Proteins
Kenta Takahashi, Yasuko Orba, Taichi Kimura, Lei Wang, Shinji Kohsaka, Masumi Tsuda, Mishie Tanino, Hiroshi Nishihara, Kazuo Nagashima, Hirofumi Sawa, Shinya Tanaka
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 66, 2, 126, 132, Mar. 2013, [Peer-reviewed]
English, Scientific journal

Population genetic analysis and sub-structuring of Theileria parva in the northern and eastern parts of Zambia
Walter Muleya, Boniface Namangala, Martin Simuunza, Ryo Nakao, Noboru Inoue, Takashi Kimura, Kimihito Ito, Chihiro Sugimoto, Hirofumi Sawa
PARASITES & VECTORS, 5, 255, Nov. 2012, [Peer-reviewed]
English, Scientific journal

Molecular surveillance and phylogenetic analysis of Old World arenaviruses in Zambia
Akihiro Ishii, Yuka Thomas, Ladslav Moonga, Ichiro Nakamura, Aiko Ohnuma, Bernard M. Hang'ombe, Ayato Takada, Aaron S. Mweene, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 93, 10, 2247, 2251, Oct. 2012, [Peer-reviewed]
English, Scientific journal

Molecular detection of a novel paramyxovirus in fruit bats from Indonesia
Michihito Sasaki, Agus Setiyono, Ekowati Handharyani, Ibenu Rahmadani, Siswatiana Taha, Sri Adiani, Mawar Subangkit, Hirofumi Sawa, Ichiro Nakamura, Takashi Kimura
VIROLOGY JOURNAL, 9, 240, Oct. 2012, [Peer-reviewed]
English, Scientific journal

Role of JC virus agnoprotein in virion formation
Tadaki Suzuki, Shingo Semba, Yuji Sunden, Yasuko Orba, Shintaro Kobayashi, Kazuo Nagashima, Takashi Kimura, Hideki Hasegawa, Hirofumi Sawa
MICROBIOLOGY AND IMMUNOLOGY, 56, 9, 639, 646, Sep. 2012, [Peer-reviewed]
English, Scientific journal

Pathological Examination of Lung Tissues in Influenza A Virus-Infected Mice
Nilton Akio Muto, Yuji Sunden, Tomoe Hattori, Daisuke Fujikura, Yosuke Nakayama, Tadaaki Miyazaki, Mitsuo Maruyama, Takashi Kimura, Hirofumi Sawa
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 65, 5, 383, 391, Sep. 2012, [Peer-reviewed]
English, Scientific journal

Accumulation of ubiquitinated proteins is related to West Nile virus-induced neuronal apoptosis
Shintaro Kobayashi, Yasuko Orba, Hiroki Yamaguchi, Takashi Kimura, Hirofumi Sawa
NEUROPATHOLOGY, 32, 4, 398, 405, Aug. 2012, [Peer-reviewed]
English, Scientific journal

Inhibitory effects of an M2-specific monoclonal antibody on different strains of influenza A virus
Nilton Akio Muto, Reiko Yoshida, Tadaki Suzuki, Shintaro Kobayashi, Hiroichi Ozaki, Daisuke Fujikura, Rashid Manzoor, Mieko Muramatsu, Ayato Takada, Takashi Kimura, Hirofumi Sawa
JAPANESE JOURNAL OF VETERINARY RESEARCH, 60, 2-3, 71, 83, Aug. 2012, [Peer-reviewed]
English, Scientific journal

Human-animal anthrax outbreak in the Luangwa valley of Zambia in 2011
Mudenda B. Hang'ombe, James C. L. Mwansa, Sergio Muwowo, Phillip Mulenga, Muzala Kapina, Eric Musenga, David Squarre, Liywali Mataa, Suzuki Y. Thomas, Hirohito Ogawa, Hirofumi Sawa, Hideaki Higashi
TROPICAL DOCTOR, 42, 3, 136, 139, Jul. 2012, [Peer-reviewed]
English, Scientific journal

Alpha-Defensin Overexpression in Patients With Bell's Palsy and Ramsay Hunt Syndrome
Yasushi Furuta, Nobuhiko Oridate, Norihito Takeichi, Satoshi Fukuda, Hirofumi Sawa
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 121, 6, 419, 425, Jun. 2012, [Peer-reviewed]
English, Scientific journal

The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice
Shigetomo Fukuhara, Szandor Simmons, Shunsuke Kawamura, Asuka Inoue, Yasuko Orba, Takeshi Tokudome, Yuji Sunden, Yuji Arai, Kazumasa Moriwaki, Junji Ishida, Akiyoshi Uemura, Hiroshi Kiyonari, Takaya Abe, Akiyoshi Fukamizu, Masanori Hirashima, Hirofumi Sawa, Junken Aoki, Masaru Ishii, Naoki Mochizuki
JOURNAL OF CLINICAL INVESTIGATION, 122, 4, 1416, 1426, Apr. 2012, [Peer-reviewed]
English, Scientific journal

JC Virus Encephalopathy Is Associated with a Novel Agnoprotein-Deletion JCV Variant
Xin Dang, Christian Wuethrich, Jennifer Gordon, Hirofumi Sawa, Igor J. Koralnik
PLOS ONE, 7, 4, e35793, Apr. 2012, [Peer-reviewed]
English, Scientific journal

A case of clear cell variant of solid-pseudopapillary tumor of the pancreas in an adult male patient.
Tanino M, Kohsaka S, Kimura T, Tabu K, Nishihara H, Sawa H, Kawami H, Kamada H, Shimizu M, Tanaka S
Annals of diagnostic pathology, 16, 2, 134, 140, Apr. 2012, [Peer-reviewed]

Molecular epidemiology and a loop-mediated isothermal amplification method for diagnosis of infection with rabies virus in Zambia
Walter Muleya, Boniface Namangala, Aaron Mweene, Luke Zulu, Paul Fandamu, Douglas Banda, Takashi Kimura, Hirofumi Sawa, Akihiro Ishii
VIRUS RESEARCH, 163, 1, 160, 168, Jan. 2012, [Peer-reviewed]
English, Scientific journal

Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia
Bernard M Hang'Ombe, Ichiro Nakamura, Kenny L Samui, Davy Kaile, Aaron S Mweene, Bukheti S Kilonzo, Hirofumi Sawa, Chihiro Sugimoto, Brendan W Wren
BMC Research Notes, 5, 72, 2012, [Peer-reviewed]
English, Scientific journal

Virus Capsid Coating of Gold Nanoparticles via Cysteine-Au Interactions and their Effective Cellular Uptakes.
Nagakawa K, Niikura K, Suzuki T, Matsuo Y, Igarashi M, Sawa H, Ijiro K
Chemistry Letters, 41, 1, 113, 115, 2012, [Peer-reviewed]
English, Scientific journal

難治性神経感染症update 進行性多巣性白質脳症
水澤 英洋, 岸田 修二, 西條 政幸, 雪下 基弘, 宍戸 由紀子[原], 澤 洋文, 長嶋 和郎, 奴久妻 聡一, 山田 正仁
臨床神経学, 51, 11, 1051, 1057, (一社)日本神経学会, Nov. 2011
Japanese

Single Amino Acid Residue in the A2 Domain of Major Histocompatibility Complex Class I Is Involved in the Efficiency of Equine Herpesvirus-1 Entry
Michihito Sasaki, Eunmi Kim, Manabu Igarashi, Kimihito Ito, Rie Hasebe, Hideto Fukushi, Hirofumi Sawa, Takashi Kimura
JOURNAL OF BIOLOGICAL CHEMISTRY, 286, 45, 39370, 39378, Nov. 2011, [Peer-reviewed]
English, Scientific journal

A novel function of the N-terminal domain of PA in assembly of influenza A virus RNA polymerase
Tadaki Suzuki, Akira Ainai, Noriyo Nagata, Tetsutaro Sata, Hirofumi Sawa, Hideki Hasegawa
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 414, 4, 719, 726, Nov. 2011, [Peer-reviewed]
English, Scientific journal

Novel Arenavirus, Zambia
Akihiro Ishii, Yuka Thomas, Ladslav Moonga, Ichiro Nakamura, Aiko Ohnuma, Bernard Hang'ombe, Ayato Takada, Aaron Mweene, Hirofumi Sawa
EMERGING INFECTIOUS DISEASES, 17, 10, 1921, 1924, Oct. 2011, [Peer-reviewed]
English, Scientific journal

ウマMHCクラスI遺伝子導入マウスのウマヘルペスウイルス1型に対する感受性　　　　　　　　　　　　　　　
木村 享史, 佐々木 道仁, 金 亨振, 福士 秀人, 澤 洋文
日本獣医学会学術集会講演要旨集, 152回, 184, 184, (公社)日本獣医学会, Aug. 2011
Japanese

Detection of KI polyomavirus and WU polyomavirus DNA by real-time polymerase chain reaction in nasopharyngeal swabs and in normal lung and lung adenocarcinoma tissues
Shinobu Teramoto, Miki Kaiho, Yasuo Takano, Rika Endo, Hideaki Kikuta, Hirofumi Sawa, Tadashi Ariga, Nobuhisa Ishiguro
MICROBIOLOGY AND IMMUNOLOGY, 55, 7, 525, 530, Jul. 2011
English, Scientific journal

Detection of KI polyomavirus and WU polyomavirus DNA by real-time polymerase chain reaction in nasopharyngeal swabs and in normal lung and lung adenocarcinoma tissues
Shinobu Teramoto, Miki Kaiho, Yasuo Takano, Rika Endo, Hideaki Kikuta, Hirofumi Sawa, Tadashi Ariga, Nobuhisa Ishiguro
MICROBIOLOGY AND IMMUNOLOGY, 55, 7, 525, 530, Jul. 2011, [Peer-reviewed]
English, Scientific journal

Characterization of influenza A viruses isolated from wild waterfowl in Zambia
Edgar Simulundu, Akihiro Ishii, Manabu Igarashi, Aaron S. Mweene, Yuka Suzuki, Bernard M. Hang'ombe, Boniface Namangala, Ladslav Moonga, Rashid Manzoor, Kimihito Ito, Ichiro Nakamura, Hirofumi Sawa, Chihiro Sugimoto, Hiroshi Kida, Chuma Simukonda, Wilbroad Chansa, Jack Chulu, Ayato Takada
JOURNAL OF GENERAL VIROLOGY, 92, 6, 1416, 1427, Jun. 2011, [Peer-reviewed]
English, Scientific journal

Paradoxical effects of chondroitin sulfate-E on Japanese encephalitis viral infection
Eunmi Kim, Megumi Okumura, Hirofumi Sawa, Tadaaki Miyazaki, Daisuke Fujikura, Shuhei Yamada, Kazuyuki Sugahara, Michihito Sasaki, Takashi Kimura
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 409, 4, 717, 722, Jun. 2011, [Peer-reviewed]
English, Scientific journal

Detection and characterization of a novel polyomavirus in wild rodents
Yasuko Orba, Shintaro Kobayashi, Ichiro Nakamura, Akihiro Ishii, Bernard M. Hang'ombe, Aaron S. Mweene, Yuka Thomas, Takashi Kimura, Hirofumi Sawa
JOURNAL OF GENERAL VIROLOGY, 92, 4, 789, 795, Apr. 2011, [Peer-reviewed]
English, Scientific journal

Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D
Michihito Sasaki, Rie Hasebe, Yoshinori Makino, Tadaki Suzuki, Hideto Fukushi, Minoru Okamoto, Kazuya Matsuda, Hiroyuki Taniyama, Hirofumi Sawa, Takashi Kimura
GENES TO CELLS, 16, 4, 343, 357, Apr. 2011, [Peer-reviewed]
English, Scientific journal

High expression of MeCP2 in JC virus-infected cells of progressive multifocal leukoencephalopathy brains
Saya Shirai, Kenta Takahashi, Shinji Kohsaka, Tetsu Tsukamoto, Hiroshi Isogai, Shinichi Kudo, Hirofumi Sawa, Kazuo Nagashima, Shinya Tanaka
NEUROPATHOLOGY, 31, 1, 38, 41, Feb. 2011, [Peer-reviewed]
English, Scientific journal

ウマヘルペスウイルス1型の新たな細胞内侵入経路(Novel entry pathway of equine herpesvirus-1)　　　　　　　　　　　　　　　
佐々木 道仁, 長谷部 理絵, 澤 洋文, 福士 秀人, 谷山 弘行
日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 83回・33回, 1P, 1055, (公社)日本生化学会, Dec. 2010
Japanese

Chondroitin sulfate-E induced enhancement of Japanese encephalitis virus infection
Kim Eunmi, Okumura Megumi, Sasaki Michihito, Fujikura Daisuke, Miyazaki Tadaaki, Sawa Hirofumi, Kimura Takashi
JOURNAL OF NEUROVIROLOGY, 16, 44, Oct. 2010, [Peer-reviewed]

Flavivirus Encephalitis: Pathological Aspects of Mouse and Other Animal Models
T. Kimura, M. Sasaki, M. Okumura, E. Kim, H. Sawa
VETERINARY PATHOLOGY, 47, 5, 806, 818, Sep. 2010
English, Scientific journal

Functional analysis of an alpha-helical antimicrobial peptide derived from a novel mouse defensin-like gene
Akira Kawaguchi, Tadaki Suzuki, Takashi Kimura, Naoki Sakai, Tokiyoshi Ayabe, Hirofumi Sawa, Hideki Hasegawa
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 398, 4, 778, 784, Aug. 2010, [Peer-reviewed]
English, Scientific journal

Functional analysis of an alpha-helical antimicrobial peptide derived from a novel mouse defensin-like gene
Akira Kawaguchi, Tadaki Suzuki, Takashi Kimura, Naoki Sakai, Tokiyoshi Ayabe, Hirofumi Sawa, Hideki Hasegawa
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 398, 4, 778, 784, Aug. 2010
English, Scientific journal

Natalizumab Has No Direct Biological Effect on JC Virus Infectivity in Permissive Human Neural Cell Lines
Tadaki Suzuki, Satoko Yamanouchi, Yuji Sunden, Yasuko Orba, Takashi Kimura, Hirofumi Sawa
JOURNAL OF MEDICAL VIROLOGY, 82, 7, 1229, 1235, Jul. 2010, [Peer-reviewed]
English, Scientific journal

Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein
Rie Hasebe, Tadaki Suzuki, Yoshinori Makino, Manabu Igarashi, Satoko Yamanouchi, Akihiko Maeda, Motohiro Horiuchi, Hirofumi Sawa, Takashi Kimura
BMC MICROBIOLOGY, 10, 165, Jun. 2010, [Peer-reviewed]
English, Scientific journal

Cytokine and Growth Factor Expression by HTLV-1 Lck-tax Transgenic Cells in SCID Mice
Karen M. Watters, Jonathan Dean, Hideki Hasegawa, Hirofumi Sawa, William Hall, Noreen Sheehy
AIDS RESEARCH AND HUMAN RETROVIRUSES, 26, 5, 593, 603, May 2010, [Peer-reviewed]
English, Scientific journal

Low pH-Triggered Model Drug Molecule Release from Virus-Like Particles
Noriko Ohtake, Kenichi Niikura, Tadaki Suzuki, Keita Nagakawa, Shintaro Mikuni, Yasutaka Matsuo, Masataka Kinjo, Hirofumi Sawa, Kuniharu Ijiro
CHEMBIOCHEM, 11, 7, 959, 962, May 2010, [Peer-reviewed]
English, Scientific journal

The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin
Tadaki Suzuki, Yasuko Orba, Yuki Okada, Yuji Sunden, Takashi Kimura, Shinya Tanaka, Kazuo Nagashima, William W. Hall, Hirofumi Sawa
PLOS PATHOGENS, 6, 3, e1000801, Mar. 2010, [Peer-reviewed]
English, Scientific journal

Induction of Cross-Protective Immunity Against Influenza A Virus H5N1 by an Intranasal Vaccine With Extracts of Mushroom Mycelia
Takeshi Ichinohe, Akira Ainai, Tomoyuki Nakamura, Yukihito Akiyama, Jun-ichi Maeyama, Takato Odagiri, Masato Tashiro, Hidehiro Takahashi, Hirofumi Sawa, Shin-ichi Tamura, Joe Chiba, Takeshi Kurata, Tetsutaro Sata, Hideki Hasegawa
JOURNAL OF MEDICAL VIROLOGY, 82, 1, 128, 137, Jan. 2010, [Peer-reviewed]
English, Scientific journal

Large T Antigen Promotes JC Virus Replication in G(2)-arrested Cells by Inducing ATM- and ATR-mediated G(2) Checkpoint Signaling
Yasuko Orba, Tadaki Suzuki, Yoshinori Makino, Kanako Kubota, Shinya Tanaka, Takashi Kimura, Hirofumi Sawa
JOURNAL OF BIOLOGICAL CHEMISTRY, 285, 2, 1544, 1554, Jan. 2010, [Peer-reviewed]
English, Scientific journal

Effects of the number of amino acid residues in the signal segment upstream or downstream of the NS2B-3 cleavage site on production and secretion of prM/M-E virus-like particles of West Nile virus
Hidehiro Takahashi, Naohiro Ohtaki, Masae Maeda-Sato, Michiko Tanaka, Keiko Tanaka, Hirofumi Sawa, Toyokazu Ishikawa, Akihisa Takamizawa, Tomohiko Takasaki, Hideki Hasegawa, Tetsutaro Sata, William W. Hall, Takeshi Kurata, Asato Kojima
MICROBES AND INFECTION, 11, 13, 1019, 1028, Nov. 2009, [Peer-reviewed]
English, Scientific journal

Covalent bonded Gag multimers in human immunodeficiency virus type-1 particles
Yoshinori Kitagawa, Masae Maeda-Sato, Keiko Tanaka, Minoru Tobiume, Hirofumi Sawa, Hideki Hasegawa, Asato Kojima, William W. Hall, Takeshi Kurata, Tetsutaro Sata, Hidehiro Takahashi
MICROBIOLOGY AND IMMUNOLOGY, 53, 11, 609, 620, Nov. 2009, [Peer-reviewed]
English, Scientific journal

Inhibition of the SDF-1 alpha-CXCR4 axis by the CXCR4 antagonist AMD3100 suppresses the migration of cultured cells from ATL patients and murine lymphoblastoid cells from HTLV-I Tax transgenic mice
Akira Kawaguchi, Yasuko Orba, Takashi Kimura, Hidekatsu Iha, Masao Ogata, Takahiro Tsuji, Akira Ainai, Tetsutaro Sata, Takashi Okamoto, William W. Hall, Hirofumi Sawa, Hideki Hasegawa
BLOOD, 114, 14, 2961, 2968, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways
Rie Hasebe, Michihito Sasaki, Hirofumi Sawa, Ryuichi Wada, Takashi Umemura, Takashi Kimura
VIROLOGY, 393, 2, 198, 209, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Gold Nanoparticle Arrangement on Viral Particles through Carbohydrate Recognition: A Non-Cross-Linking Approach to Optical Virus Detection
Kenichi Niikura, Keita Nagakawa, Noriko Ohtake, Tadaki Suzuki, Yasutaka Matsuo, Hirofumi Sawa, Kuniharu Ijiro
BIOCONJUGATE CHEMISTRY, 20, 10, 1848, 1852, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Characterization of H3N6 avian influenza virus isolated from a wild white pelican in Zambia
Edgar Simulundu, Aaron S. Mweene, Daisuke Tomabechi, Bernard M. Hang'ombe, Akihiro Ishii, Yuka Suzuki, Ichiro Nakamura, Hirofumi Sawa, Chihiro Sugimoto, Kimihito Ito, Hiroshi Kida, Lewis Saiwana, Ayato Takada
ARCHIVES OF VIROLOGY, 154, 9, 1517, 1522, Sep. 2009, [Peer-reviewed]
English, Scientific journal

Adaptor Protein Crk Induces Src-Dependent Activation of p38 MAPK in Regulation of Synovial Sarcoma Cell Proliferation
Takuya Watanabe, Masumi Tsuda, Shinya Tanaka, Yusuke Ohba, Hideaki Kawaguchi, Tokifumi Majima, Hirofumi Sawa, Akio Minami
MOLECULAR CANCER RESEARCH, 7, 9, 1582, 1592, Sep. 2009, [Peer-reviewed]
English, Scientific journal

Human synovial sarcoma proto-oncogene Syt is essential for early embryonic development through the regulation of cell migration
Taichi Kimura, Mieko Sakai, Kouichi Tabu, Lei Wang, Ryosuke Tsunematsu, Masumi Tsuda, Hirofumi Sawa, Kazuo Nagashima, Hiroshi Nishihara, Shigetsugu Hatakeyama, Keiko Nakayama, Marc Ladanyi, Shinya Tanaka, Keiichi I. Nakayama
LABORATORY INVESTIGATION, 89, 6, 645, 656, Jun. 2009, [Peer-reviewed]
English, Scientific journal

A case of central nervous system lymphomatoid granulomatosis; characteristics of PET imaging and pathological findings.
Nishihara H, Nakasato M, Sawa H, Murakami H, Yamamoto D, Moriyama K, Kato N, Hashimoto I, Kamada H, Tanaka S
Journal of neuro-oncology, 93, 275, 278, 2, Jun. 2009, [Peer-reviewed]

Monoclonal Antibody and siRNAs for Topoisomerase I Suppress Telomerase Activity
Hidehiro Takahashi, Yoshinori Kitagawa, Masae Maeda-Satoh, Hideki Hasegawa, Hirofumi Sawa, Tetsutaro Sata
HYBRIDOMA, 28, 1, 63, 65, Feb. 2009, [Peer-reviewed]
English, Scientific journal

Monoclonal Antibody and siRNAs for Topoisomerase I Suppress Telomerase Activity
Hidehiro Takahashi, Yoshinori Kitagawa, Masae Maeda-Satoh, Hideki Hasegawa, Hirofumi Sawa, Tetsutaro Sata
HYBRIDOMA, 28, 1, 63, 65, Feb. 2009
English, Scientific journal

An siRNA against JC virus (JCV) agnoprotein inhibits JCV infection in JCV-producing cells inoculated in nude mice
Tomoko Matoba, Yasuko Orba, Tadaki Suzuki, Yoshinori Makino, Hideo Shichinohe, Satoshi Kuroda, Takahiro Ochiya, Hiroshi Itoh, Shinya Tanaka, Kazuo Nagashima, Hirofumi Sawa
NEUROPATHOLOGY, 28, 3, 286, 294, Jun. 2008, [Peer-reviewed]
English, Scientific journal

Proteomics- and transcriptomics-based screening of differentially expressed proteins and genes in brain of Wig rat: A model for attention deficit hyperactivity disorder (ADHD) research
Misato Hirano, Randeep Rakwal, Junko Shibato, Hirofumi Sawa, Kazuo Nagashima, Yoko Ogawa, Yasukazu Yoshida, Hitoshi Wahashi, Etsuo Niki, Yoshinori Masuo
JOURNAL OF PROTEOME RESEARCH, 7, 6, 2471, 2489, Jun. 2008, [Peer-reviewed]
English

Progressive multifocal leukoencephalopathy and CD4+T-lymphocytopenia in a patient with Sjogren syndrome
Yuichi Hayashi, Akio Kimura, Shimon Kato, Akihiro Koumura, Takeo Sakurai, Yuji Tanaka, Isao Hozumi, Yuji Sunden, Yasuko Orba, Hirofumi Sawa, Hitoshi Takahashi, Takashi Inuzuka
JOURNAL OF THE NEUROLOGICAL SCIENCES, 268, 1-2, 195, 198, May 2008, [Peer-reviewed]
English, Scientific journal

Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure
Jun Nakae, Yongheng Cao, Miyo Oki, Yasuko Orba, Hirofumi Sawa, Hiroshi Kiyonari, Kristy Iskandar, Koji Suga, Marc Lombes, Yoshitake Hayashi
DIABETES, 57, 3, 563, 576, Mar. 2008, [Peer-reviewed]
English, Scientific journal

Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure
Jun Nakae, Yongheng Cao, Miyo Oki, Yasuko Orba, Hirofumi Sawa, Hiroshi Kiyonari, Kristy Iskandar, Koji Suga, Marc Lombes, Yoshitake Hayashi
DIABETES, 57, 3, 563, 576, Mar. 2008
English, Scientific journal

Enhanced cellular uptake of virus-like particles through immobilization on a sialic acid-displaying solid surface
Noriko Ohtake, Kenichi Niikura, Tadaki Suzuki, Keita Nagakawa, Hirofumi Sawa, Kuniharu Ijiro
BIOCONJUGATE CHEMISTRY, 19, 2, 507, 515, Feb. 2008, [Peer-reviewed]
English, Scientific journal

Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse
Naomi Ohnishi, Hitomi Yuasa, Shinya Tanaka, Hirofumi Sawa, Motohiro Miura, Atsushi Matsui, Hideaki Higashi, Manabu Musashi, Kazuya Lwabuchi, Misao Suzuki, Gen Yamada, Takeshi Azuma, Masanori Hatakeyama
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105, 3, 1003, 1008, Jan. 2008, [Peer-reviewed]
English, Scientific journal

Pharmacological cdk inhibitor R-Roscovitine suppresses JC virus proliferation
Yasuko Orba, Yuji Sunden, Tadaki Suzuki, Kazuo Nagashima, Takashi Kimura, Shinya Tanaka, Hirofumi Sawa
VIROLOGY, 370, 1, 173, 183, Jan. 2008, [Peer-reviewed]
English, Scientific journal

Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine
Takeshi Ichinohe, Shin-ichi Tamura, Akira Kawaguchi, Ai Ninomiya, Masaki Imai, Shigeyuki Itamura, Takato Odagiri, Masato Tashiro, Hidehiro Takahashi, Hirofumi Sawa, William M. Mitchell, David R. Strayer, William A. Carter, Joe Chiba, Takeshi Kurata, Tetsutaro Sata, Hideki Hasegawa
JOURNAL OF INFECTIOUS DISEASES, 196, 9, 1313, 1320, Nov. 2007, [Peer-reviewed]
English, Scientific journal

Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine
Takeshi Ichinohe, Shin-ichi Tamura, Akira Kawaguchi, Ai Ninomiya, Masaki Imai, Shigeyuki Itamura, Takato Odagiri, Masato Tashiro, Hidehiro Takahashi, Hirofumi Sawa, William M. Mitchell, David R. Strayer, William A. Carter, Joe Chiba, Takeshi Kurata, Tetsutaro Sata, Hideki Hasegawa
JOURNAL OF INFECTIOUS DISEASES, 196, 9, 1313, 1320, Nov. 2007
English, Scientific journal

Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA
Kouichi Tabu, Yusuke Ohba, Tadaki Suzuki, Yoshinori Makino, Taichi Kimura, Akiko Ohnishi, Mieko Sakai, Takuya Watanabe, Shinya Tanaka, Hirofumi Sawa
MOLECULAR CANCER RESEARCH, 5, 10, 1099, 1109, Oct. 2007, [Peer-reviewed]
English, Scientific journal

A case of highly active anti-retroviral therapy-induced immune reconstitution inflammatory syndrome in AIDS-related progressive multifocal leukoencephalopathy
Eiji Imamura, Hiroshi Yamashita, Toshiyuki Fukuhara, Hirofumi Sawa, Kazuo Nagashima, Masao Kuwabara, Hiroshi Tokinobu
Clinical Neurology, 47, 10, 650, 656, 10, Oct. 2007, [Peer-reviewed]
Japanese, Scientific journal

Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA
Kouichi Tabu, Yusuke Ohba, Tadaki Suzuki, Yoshinori Makino, Taichi Kimura, Akiko Ohnishi, Mieko Sakai, Takuya Watanabe, Shinya Tanaka, Hirofumi Sawa
MOLECULAR CANCER RESEARCH, 5, 10, 1099, 1109, Oct. 2007
English, Scientific journal

Axonal guidance protein FEZ1 associates with tubulin and kinesin motor protein to transport mitochondria in neurites of NGF-stimulated PC12 cells
Toshitsugu Ftijita, Andres D. Maturana, Junko Ikuta, Juri Hamada, Sebastien Walchli, Tadaki Suzuki, Hirofumi Sawa, Marie W. Wooten, Toshihide Okajima, Kenji Taternatsu, Katsuyuki Tanizawa, Shun'ichi Kuroda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 361, 3, 605, 610, Sep. 2007, [Peer-reviewed]
English, Scientific journal

Intranasal immunization with H5N1 vaccine plus Poly I : Poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge
Takeshi Ichinohe, Akira Kawaguchi, Shin-ichi Tamura, Hidehiro Takahashi, Hirofumi Sawa, Ai Ninomiya, Masaki Imai, Shigeyuki Itamura, Takato Odagiri, Masato Tashiro, Joe Chiba, Tetsutaro Sata, Takeshi Kurata, Hideki Hasegawa
MICROBES AND INFECTION, 9, 11, 1333, 1340, Sep. 2007, [Peer-reviewed]
English, Scientific journal

[Etiological agent and pathogenicity mechanism of PML].
Suzuki T, Nagashima K, Sawa H
Nihon rinsho. Japanese journal of clinical medicine, 65, 1495, 1500, 8, Aug. 2007, [Peer-reviewed]

Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling
Yoshikazu Nakaoka, Keigo Nishida, Masahiro Narimatsu, Atsunori Kamiya, Takashi Minami, Hirofumi Sawa, Katsuya Okawa, Yasushi Fujio, Tatsuya Koyama, Makiko Maeda, Manami Sone, Satoru Yamasaki, Yuji Arai, Gou Young Koh, Tatsuhiko Kodama, Hisao Hirota, Kinya Otsu, Toshio Hirano, Naoki Mochizuki
JOURNAL OF CLINICAL INVESTIGATION, 117, 7, 1771, 1781, Jul. 2007, [Peer-reviewed]
English, Scientific journal

Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus
Takeshi Ichinohe, Noriyo Nagata, Peter Strong, Shin-ichi Tamura, Hidehiro Takahashi, Ai Ninomiya, Masaki Imai, Takato Odagiri, Masato Tashiro, Hirofumi Sawa, Joe Chiba, Takeshi Kurata, Tetsutaro Sata, Hideki Hasegawa
JOURNAL OF MEDICAL VIROLOGY, 79, 6, 811, 819, Jun. 2007, [Peer-reviewed]
English, Scientific journal

Behavioural characteristics and gene expression in the hyperactive wiggling (Wig) rat
Yoshinori Masuo, Masami Ishido, Masatoshi Morita, Hirofumi Sawa, Kazuo Nagashima, Etsuo Niki
EUROPEAN JOURNAL OF NEUROSCIENCE, 25, 12, 3659, 3666, Jun. 2007, [Peer-reviewed]
English, Scientific journal

The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent
Takahiro Tsuji, Noreen Sheehy, Virginie W. Gautier, Hitoshi Hayakawa, Hirofumi Sawa, William W. Hall
JOURNAL OF BIOLOGICAL CHEMISTRY, 282, 18, 13875, 13883, May 2007, [Peer-reviewed]
English, Scientific journal

R-ras regulates exocytosis by Rgl2/Rlf-mediated activation of RalA on endosomes
Akiyuki Takaya, Takahiro Kamio, Michitaka Masuda, Naoki Mochizuki, Hirofumi Sawa, Mami Sato, Kazuo Nagashima, Akiko Mizutani, Akira Matsuno, Etsuko Kiyokawa, Michiyuki Matsuda
MOLECULAR BIOLOGY OF THE CELL, 18, 5, 1850, 1860, May 2007, [Peer-reviewed]
English, Scientific journal

[Recent research on the JC virus].
Sawa H, Suzuki T, Orba Y, Sunden Y, Nagashima K
Brain and nerve = Shinkei kenkyu no shinpo, 59, 101, 108, 2, Feb. 2007, [Peer-reviewed]

Lamprey TLRs with properties distinct from those of the variable lymphocyte receptors
Akihiro Ishii, Aya Matsuo, Hirofumi Sawa, Tadayuki Tsujita, Kyoko Shida, Misako Matsumoto, Tsukasa Seya
JOURNAL OF IMMUNOLOGY, 178, 1, 397, 406, Jan. 2007, [Peer-reviewed]
English, Scientific journal

Identification of DDX1 as a JC virus transcriptional control region-binding protein
Yuji Sunden, Shingo Semba, Tadaki Suzuki, Yuki Okada, Yasuko Orba, Kazuo Nagashima, Takashi Umemura, Hirofumi Sawa
MICROBIOLOGY AND IMMUNOLOGY, 51, 3, 327, 337, 2007, [Peer-reviewed]
English, Scientific journal

DDX1 promotes proliferation of the JC virus through transactivation of its promoter
Yuji Sunden, Shingo Semba, Tadaki Suzuki, Yuki Okada, Yasuko Orba, Kazuo Nagashima, Takashi Umemura, Hirofumi Sawa
MICROBIOLOGY AND IMMUNOLOGY, 51, 3, 339, 347, 2007, [Peer-reviewed]
English, Scientific journal

高活性レトロウイルス療法により免疫再構築症候群をきたしたAIDSにともなう進行性多巣性白質脳症の1剖検例　　　　　　　　　　　　　　　
臨床神経学, 65, 1495, 1500, 2007

進行性多巣性白質脳症 （PML）：原因ウイルスと発病機構。　　　　　　　　　　　　　　　
日本臨床, 65, 1495, 1500, 2007

Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection
Yasuko Asahi-Ozaki, Shigeyuki Itamura, Takeshi Ichinohe, Peter Strong, Shin-ichi Tamura, Hidehiro Takahashi, Hirofumi Sawa, Masami Moriyama, Masato Tashiro, Tetsutaro Sata, Takeshi Kurata, Hideki Hasegawa
MICROBES AND INFECTION, 8, 12-13, 2706, 2714, Oct. 2006, [Peer-reviewed]
English, Scientific journal

Tristetraprolin inhibits HIV-1 production by binding to genomic RNA
Masae Maeda, Hirofumi Sawa, Minoru Tobiume, Kenzo Tokunaga, Hideki Hasegawa, Takeshi Ichinohe, Tetsutaro Sata, Masami Moriyama, William W. Hall, Takeshi Kurata, Hidehiro Takahashi
MICROBES AND INFECTION, 8, 11, 2647, 2656, Sep. 2006, [Peer-reviewed]
English, Scientific journal

Protection against influenza virus infection by intranasal vaccine with surf clam microparticles (SMP) as an adjuvant
T Ichinohe, Watanabe, I, E Tao, S Ito, A Kawaguchi, S Tamura, H Takahashi, H Sawa, M Moriyama, J Chiba, K Komase, Y Suzuki, T Kurata, T Sata, H Hasegawa
JOURNAL OF MEDICAL VIROLOGY, 78, 7, 954, 963, Jul. 2006, [Peer-reviewed]
English, Scientific journal

Adaptor molecule Crk is required for sustained phosphorylation of Grb2-associated binder 1 and hepatocyte growth factor-induced cell motility of human synovial sarcoma cell lines
Takuya Watanabe, Masumi Tsuda, Yoshinori Makino, Shin Ichihara, Hirofumi Sawa, Akio Minami, Naoki Mochizuki, Kazuo Nagashima, Shinya Tanaka
MOLECULAR CANCER RESEARCH, 4, 7, 499, 510, Jul. 2006, [Peer-reviewed]
English, Scientific journal

Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS
H Linghu, M Tsuda, Y Makino, M Sakai, T Watanabe, S Ichihara, H Sawa, K Nagashima, N Mochizuki, S Tanaka
ONCOGENE, 25, 25, 3547, 3556, Jun. 2006
English, Scientific journal

Characterization and application of polyclonal antibodies that specifically recognize JC virus large T antigen
Y Sunden, T Suzuki, Y Orba, T Umemura, M Asamoto, K Nagashima, S Tanaka, H Sawa
ACTA NEUROPATHOLOGICA, 111, 4, 379, 387, Apr. 2006, [Peer-reviewed]
English, Scientific journal

Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human T-lymphotropic virus type I
H Hasegawa, H Sawa, MJ Lewis, Y Orba, N Sheehy, Y Yamamoto, T Ichinohe, Y Tsunetsugu-Yokota, H Katano, H Takahashi, J Matsuda, T Sata, T Kurata, K Nagashima, WW Hall
NATURE MEDICINE, 12, 4, 466, 472, Apr. 2006, [Peer-reviewed]
English, Scientific journal

A novel function of OLIG2 to suppress human glial tumor cell growth via p27(Kip1) transactivation
K Tabu, A Ohnishi, Y Sunden, T Suzuki, M Tsuda, S Tanaka, T Sakai, K Nagashima, H Sawa
JOURNAL OF CELL SCIENCE, 119, 7, 1433, 1441, Apr. 2006, [Peer-reviewed]
English, Scientific journal

Elmo1 inhibits ubiquitylation of Dock180
Y Makino, M Tsuda, S Ichihara, T Watanabe, M Sakai, H Sawa, K Nagashima, S Hatakeyama, S Tanaka
JOURNAL OF CELL SCIENCE, 119, 5, 923, 932, Mar. 2006, [Peer-reviewed]
English, Scientific journal

Dicer and positive charge of proteins decrease the stability of RNA containing the AU-rich element of GM-CSF
H Takahashi, M Maeda, H Sawa, H Hasegawa, M Moriyama, T Sata, WW Hall, T Kurata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 340, 3, 807, 814, Feb. 2006, [Peer-reviewed]
English, Scientific journal

Induction of p21(WAF1/CIP1) by human synovial sarcoma-associated chimeric oncoprotein SYT-SSX1
M Tsuda, T Watanabe, T Seki, T Kimura, H Sawa, A Minami, T Akagi, K Isobe, K Nagashima, S Tanaka
ONCOGENE, 24, 54, 7984, 7990, Dec. 2005, [Peer-reviewed]
English, Scientific journal

Strategic Approach to Information Security and Assurance in Health Research
Shunichi Akazawa, Manabu Igarashi, Hirofumi Sawa, Hiko Tamashiro
Environmental Health and Preventive Medicine, 10, 5, 282, 285, 5, Sep. 2005, [Peer-reviewed]
English

The agnoprotein of polyomaviruses: A multifunctional auxiliary protein
K Khalili, MK White, H Sawa, K Nagashima, M Safak
JOURNAL OF CELLULAR PHYSIOLOGY, 204, 1, 1, 7, Jul. 2005, [Peer-reviewed]
English

Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules - Role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation
T Suzuki, Y Okada, S Semba, Y Orba, S Yamanouchi, S Endo, S Tanaka, T Fujita, S Kuroda, K Nagashima, H Sawa
JOURNAL OF BIOLOGICAL CHEMISTRY, 280, 26, 24948, 24956, Jul. 2005, [Peer-reviewed]
English, Scientific journal

Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules - Role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation
T Suzuki, Y Okada, S Semba, Y Orba, S Yamanouchi, S Endo, S Tanaka, T Fujita, S Kuroda, K Nagashima, H Sawa
JOURNAL OF BIOLOGICAL CHEMISTRY, 280, 26, 24948, 24956, Jul. 2005
English, Scientific journal

Dissociation of heterochromatin protein 1 from lamin B receptor induced by human polyomavirus agnoprotein: role in nuclear egress of viral particles
Y Okada, T Suzuki, Y Sunden, Y Orba, S Kose, N Imamoto, H Takahashi, S Tanaka, WW Hall, K Nagashima, H Sawa
EMBO REPORTS, 6, 5, 452, 457, May 2005, [Peer-reviewed]
English, Scientific journal

Clinicopathological and virological analyses of familial human T-lymphotropic virus type I-associated polyneuropathy
H Sawa, T Nagashima, K Nagashima, T Shinohara, T Chuma, Y Mano, N Tachi, WW Hall
JOURNAL OF NEUROVIROLOGY, 11, 2, 199, 207, Apr. 2005, [Peer-reviewed]
English, Scientific journal

Synthetic double-stranded RNA poly(I : C) combined with mucosal vaccine protects against influenza virus infection
T Ichinohe, Watanabe, I, S Ito, H Fujii, M Moriyama, S Tamura, H Takahashi, H Sawa, J Chiba, T Kurata, T Sata, H Hasegawa
JOURNAL OF VIROLOGY, 79, 5, 2910, 2919, Mar. 2005, [Peer-reviewed]
English, Scientific journal

Establishment of an immunoscreening system using recombinant VP1 protein for the isolation of a monoclonal antibody that blocks JC virus infection
C Henmi, H Sawa, H Iwata, Y Orba, S Tanaka, K Nagashima
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 327, 1, 242, 251, Feb. 2005, [Peer-reviewed]
English, Scientific journal

The JC virus-like particle overlay assay.
Sawa H, Komagome R
Methods in molecular biology (Clifton, N.J.), 292, 175, 186, 2005, [Peer-reviewed]

Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant
H Hasegawa, T Ichinohe, P Strong, Watanabe, I, S Ito, S Tamura, H Takahashi, H Sawa, J Chiba, T Kurata, T Sata
JOURNAL OF MEDICAL VIROLOGY, 75, 1, 130, 136, Jan. 2005, [Peer-reviewed]
English, Scientific journal

Sawa H, Nagashima T, Nagashima K, Shinohara T, Chuma T, Mano Y, Tachi N, Hall WW. Clinicopathological and virological analyses of familial HTLV-I associated polyneuropathy. J Neurovirol 11: 199-207, 2005*　　　　　　　　　　　　　　　
2005

Hasegawa H, Ichinohe T, Strong P, Watanabe I, Ito S, Tamura S-i, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T: Protection against influenza virus infection by intranasal administration of HA vaccine with chitin microparticles as an adjuvant. J Med V・・・　　　　　　　　　　　　　　　
2005
Hasegawa H, Ichinohe T, Strong P, Watanabe I, Ito S, Tamura S-i, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T: Protection against influenza virus infection by intranasal administration of HA vaccine with chitin microparticles as an adjuvant. J Med Virol 75: 130-136, 2005

Henmi C, Sawa H*, Iwata H, Orba Y, Tanaka S, Nagashima K: Isolation of a monoclonal antibody recognizing a cell-surface molecule as a receptor for JC virus. Biochem Biophys Res Commun 327: 242-251, 2005 (* corresponding author)*　　　　　　　　　　　　　　　
2005

Ichinohe T, Watanabe I, Ito S, Moriyama M, Tamura S, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T, Hasegawa H: Synthetic double-stranded RNA [poly (I:C)] combined with mucosal vaccine protects against influenza virus infection. J Virol 79: 2910-2919・・・　　　　　　　　　　　　　　　
2005
Ichinohe T, Watanabe I, Ito S, Moriyama M, Tamura S, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T, Hasegawa H: Synthetic double-stranded RNA [poly (I:C)] combined with mucosal vaccine protects against influenza virus infection. J Virol 79: 2910-2919, 2005*

Khalili K, White MK, Sawa H, Nagashima K, Safak M: The agnoprotein of polyomaviruses: A multifunctional auxiliary protein. J Cell Physiol 204:1-7, 2005*　　　　　　　　　　　　　　　
2005

Okada Y, Suzuki T, Sunden Y, Orba Y, Kose S, Imamoto N, Takahashi H, Tanaka S, Hall WW, Nagashima K, Sawa H*: Dissociation of heterochromatin protein 1 from lamin B receptor induced by human polyomavirus agnoprotein: role in nuclear egress of viral par・・・　　　　　　　　　　　　　　　
2005
Okada Y, Suzuki T, Sunden Y, Orba Y, Kose S, Imamoto N, Takahashi H, Tanaka S, Hall WW, Nagashima K, Sawa H*: Dissociation of heterochromatin protein 1 from lamin B receptor induced by human polyomavirus agnoprotein: role in nuclear egress of viral particles. EMBO Rep 6: 452-457, 2005 (* corresponding author)*

Akazawa S, Igarashi M, Sawa H, Tamashiro H: Strategic approach to information security and assurance in health research. Environ Health Prev Med 10: 282-285, 2005　　　　　　　　　　　　　　　
2005

Tsuda M, Watanabe T, Seki T, Kimura T, Sawa H, Minami A, Akagi T, Isobe KI, Nagashima K, Tanaka S: Induction of p21(WAF1/CIP1) by human synovial sarcoma-associated chimeric oncoprotein SYT-SSX1. Oncogene. 24: 7984-7990, 2005*　　　　　　　　　　　　　　　
2005

Investigation of Simian virus 40 large T antigen in 18 autopsied malignant mesothelioma patients in Japan
M Jin, H Sawa, T Suzuki, K Shimizu, Y Makino, S Tanaka, T Nojima, Y Fujioka, M Asamoto, N Suko, M Fujita, K Nagashima
JOURNAL OF MEDICAL VIROLOGY, 74, 4, 668, 676, Dec. 2004, [Peer-reviewed]
English, Scientific journal

Dysferlinopathy associated with rigid spine syndrome
T Nagashima, T Chuma, Y Mano, Y Goto, YK Hayashi, N Minami, Nishino, I, Nonaka, I, T Takahashi, H Sawa, M Aoki, K Nagashima
NEUROPATHOLOGY, 24, 4, 341, 346, Dec. 2004, [Peer-reviewed]
English, Scientific journal

Crk associates with ERM proteins and promotes cell motility toward hyaluronic acid
M Tsuda, Y Makino, T Iwahara, H Nishihara, H Sawa, K Nagashima, H Hanafusa, S Tanaka
JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 45, 46843, 46850, Nov. 2004, [Peer-reviewed]
English, Scientific journal

Variable patterns of varicella-zoster virus reactivation in Ramsay Hunt syndrome
H Aizawa, F Ohtani, Y Furuta, H Sawa, S Fukuda
JOURNAL OF MEDICAL VIROLOGY, 74, 2, 355, 360, Oct. 2004, [Peer-reviewed]
English, Scientific journal

A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis
Y Kamioka, S Fukuhara, H Sawa, J Nagashima, M Masuda, M Matsuda, N Mochizuki
JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 38, 40091, 40099, Sep. 2004, [Peer-reviewed]
English, Scientific journal

Varicella-zoster virus DNA level and facial paralysis in Ramsay Hunt syndrome
Y Furuta, H Aizawa, F Ohtani, H Sawa, S Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 113, 9, 700, 705, Sep. 2004, [Peer-reviewed]
English, Scientific journal

Clinico-pathological features of pilomyxoid astrocytoma of the optic pathway
K Chikai, A Ohnishi, T Kato, J Ikeda, Y Sawamura, Y Iwasaki, T Itoh, H Sawa, K Nagashima
ACTA NEUROPATHOLOGICA, 108, 2, 109, 114, Aug. 2004, [Peer-reviewed]
English, Scientific journal

Modulation of collagen fibrillogenesis by tenascin-X and type VI collagen
T Minamitani, T Ikuta, Y Saito, G Takebe, M Sato, H Sawa, T Nishimura, F Nakamura, K Takahashi, H Ariga, K Matsumoto
EXPERIMENTAL CELL RESEARCH, 298, 1, 305, 315, Aug. 2004, [Peer-reviewed]
English, Scientific journal

Triglyceride accumulation and altered composition of triglyceride-associated fatty acids in the skin of tenascin-X-deficient mice
K Matsumoto, T Sato, S Oka, Y Orba, H Sawa, K Kabayama, J Inokuchi, H Ariga
GENES TO CELLS, 9, 8, 737, 748, Aug. 2004, [Peer-reviewed]
English, Scientific journal

Triglyceride accumulation and altered composition of triglyceride-associated fatty acids in the skin of tenascin-X-deficient mice
Ken-Ichi Matsumoto, Takashige Sato, Seiko Oka, Yasuko Orba, Hirofumi Sawa, Kazuya Kabayama, Jin-Ichi Inokuchi, Hiroyoshi Ariga
Genes to Cells, 9, 8, 737, 748, Aug. 2004
English, Scientific journal

Inhibition of virus production in JC virus-infected cells by postinfection RNA interference
Y Orba, H Sawa, H Iwata, S Tanaka, K Nagashima
JOURNAL OF VIROLOGY, 78, 13, 7270, 7273, Jul. 2004, [Peer-reviewed]
English, Scientific journal

Induction of matrix metalloproteinase-2 by tenascin-X deficiency is mediated through the c-Jun N-terminal kinase and protein tyrosine kinase phosphorylation pathway
K Matsumoto, T Minamitani, Y Orba, M Sato, H Sawa, H Ariga
EXPERIMENTAL CELL RESEARCH, 297, 2, 404, 414, Jul. 2004, [Peer-reviewed]
English, Scientific journal

Nuclear entry mechanism of the human polyomavirus JC virus-like particle - Role of importins and the nuclear pore complex
QM Qu, H Sawa, T Suzuki, S Semba, C Henmi, Y Okada, M Tsuda, S Tanaka, WJ Atwood, K Nagashima
JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 26, 27735, 27742, Jun. 2004, [Peer-reviewed]
English, Scientific journal

Topoisomerase I dissociates human immunodeficiency virus type 1 reverse transcriptase from genomic RNAs
H Takahashi, H Sawa, H Hasegawa, K Nagashima, T Sata, T Kurata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 313, 4, 1073, 1078, Jan. 2004, [Peer-reviewed]
English, Scientific journal

Nucleolin and the packaging signal, psi, promote the budding of human immunodeficiency virus type-1 (HIV-1)
T Ueno, K Tokunaga, H Sawa, M Maeda, J Chiba, A Kojima, H Hasegawa, Y Shoya, T Sata, T Kurata, H Takahashi
MICROBIOLOGY AND IMMUNOLOGY, 48, 2, 111, 118, 2004, [Peer-reviewed]
English, Scientific journal

Qu Q, Sawa H*, Suzuki T, Semba S, Henmi C, Okada Y, Tsuda M, Tanaka S, Nagashima K: Nuclear entry mechanism of the human polyomavirus JC virus like particle: role of importins and the nuclear pore complex. J Biol Chem 279: 27735-27742, 2004 (* corresp・・・　　　　　　　　　　　　　　　
2004
Qu Q, Sawa H*, Suzuki T, Semba S, Henmi C, Okada Y, Tsuda M, Tanaka S, Nagashima K: Nuclear entry mechanism of the human polyomavirus JC virus like particle: role of importins and the nuclear pore complex. J Biol Chem 279: 27735-27742, 2004 (* corresponding author)*

Minamitani T, Ikuta T, Saito Y, Takebe G, Sato M, Sawa H, Nishimura T, Nakamura F, Takahashi K, Ariga H, Matsumoto K: Modulation of collagen fibrillogenesis by tenascin-X and type VI collagen. Exp Cell Res 298: 305-15, 2004*　　　　　　　　　　　　　　　
2004

Kamioka Y, Fukuhara S, Sawa H, Nagashima K, Masuda M, Matsuda M, Mochizuki N: A novel dynamin-associating molecule, formin-binding Protein 17, induces tubular membrane invaginations and participates in endocytosis. J Biol Chem 279: 40091-40099, 2004*　　　　　　　　　　　　　　　
2004

Matsumoto K, Minamitani T, Orba Y, Sato M, Sawa H, Ariga H: Induction of matrix metalloproteinase-2 by tenascin-X deficiency is mediated through the c-Jun N-terminal kinase and protein tyrosine kinase phosphorylation pathway. Exp Cell Res 297: 404-414・・・　　　　　　　　　　　　　　　
2004
Matsumoto K, Minamitani T, Orba Y, Sato M, Sawa H, Ariga H: Induction of matrix metalloproteinase-2 by tenascin-X deficiency is mediated through the c-Jun N-terminal kinase and protein tyrosine kinase phosphorylation pathway. Exp Cell Res 297: 404-414, 2004*

Tsuda M, Makino Y, Iwahara T, Nishihara H, Sawa H, Nagashima K, Hanafusa H, Tanaka S: Crk associates with ERM proteins and promotes cell motility toward hyaluronic acid. J Biol Chem 279: 46843-46850, 2004*　　　　　　　　　　　　　　　
2004

Orba Y, Sawa H*, Iwata H, Tanaka S, Nagashima K: Inhibition of virus production in JC virus-infected cells by postinfection RNA interference. J Virol 78: 7270-7273, 2004 (* corresponding author)*　　　　　　　　　　　　　　　
2004

Furuta Y, Aizawa H, Ohtani F, Sawa H, Fukuda S: Varicella-zoster virus DNA level and facial paralysis in Ramsay Hunt syndrome. Ann Otol Rhinol Laryngol 113: 700-705, 2004.*　　　　　　　　　　　　　　　
2004

Jin M, Sawa H*, Suzuki T, Shimizu K, Makino Y, Tanaka S, Nojima T, Fujioka Y, Asamoto M, Suko N, Nagashima K: Investigation of simian virus 40 large T antigen in 18 autopsied malignant mesothelioma patients in Japan. J Med Virol 74: 668-676, 2004 (* ・・・　　　　　　　　　　　　　　　
2004
Jin M, Sawa H*, Suzuki T, Shimizu K, Makino Y, Tanaka S, Nojima T, Fujioka Y, Asamoto M, Suko N, Nagashima K: Investigation of simian virus 40 large T antigen in 18 autopsied malignant mesothelioma patients in Japan. J Med Virol 74: 668-676, 2004

(* corresponding author)*

Aizawa H, Ohtani F, Furuta Y, Sawa H, Fukuda S: Variable patterns of varicella-zoster virus reactivation in Ramsay Hunt syndrome. J Med Virol 74: 355-360, 2004.*　　　　　　　　　　　　　　　
2004

Ueno T, Tokunaga K, Sawa H, Maeda M, Chiba J, Kojima A, Hasegawa H, Shoya Y, Sata T, Kutrata T, Takahashi H: Nucleolin and the packaging signal,  promote the budding of human immunodeficiency virus type-1 (HIV-1). Microbiol Immunol 48: 111-118, 2004*　　　　　　　　　　　　　　　
2004

Takahashi H, Sawa H, Hasegawa H, Nagashima K, Sata T, Kurata T: Topoisomerase I dissociates human immunodeficiency virus type 1 reverse transcriptase from genomic RNAs. Biochem Biophys Res Commun. 313: 1073-1078, 2004.*　　　　　　　　　　　　　　　
2004

Nagashima T, Chuma T, Mano Y, Goto Y-i, Hayashi KY, Minami N, Nishino I, Nonaka I, Takahashi T, Sawa H, Aoki M, Nagashima K: Dysferlinopathy associated with rigid spine syndrome. Neuropathology 24: 341-346, 2004.*　　　　　　　　　　　　　　　
2004

Chikai K, Ohnishi A, kato T, Ikeda J, Sawamura Y, Iwasaki Y, Itoh T, Sawa H, Nagashima K: Clinico-pathological features of piloymyxoid astrocytoma of the optic pathway. Acta Neuropathol 108: 109-114, 2004*　　　　　　　　　　　　　　　
2004

Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia
T Teramoto, H Kaneko, M Funato, H Sawa, K Nagashima, Y Hirose, N Kondo
SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 35, 11-12, 909, 910, Dec. 2003, [Peer-reviewed]
English, Scientific journal

Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin
Watanabe, I, TM Ross, S Tamura, T Ichinohe, S Ito, H Takahashi, H Sawa, J Chiba, T Kurata, T Sata, H Hasegawa
VACCINE, 21, 31, 4532, 4538, Nov. 2003, [Peer-reviewed]
English, Scientific journal

Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus
L Ricciardiello, M Baglioni, C Giovannini, M Pariali, G Cenacchi, A Ripalti, MP Landini, H Sawa, K Nagashima, RJ Frisque, A Goel, CR Boland, M Tognon, E Roda, F Bazzoli
CANCER RESEARCH, 63, 21, 7256, 7262, Nov. 2003, [Peer-reviewed]
English, Scientific journal

Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin
Watanabe, I, TM Ross, S Tamura, T Ichinohe, S Ito, H Takahashi, H Sawa, J Chiba, T Kurata, T Sata, H Hasegawa
VACCINE, 21, 31, 4532, 4538, Nov. 2003
English, Scientific journal

Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas
A Ohnishi, H Sawa, M Tsuda, Y Sawamura, T Itoh, Y Iwasaki, K Nagashima
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 62, 10, 1052, 1059, Oct. 2003, [Peer-reviewed]
English, Scientific journal

Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome
T Nagashima, Y Mizutani, H Kawahara, S Maguchi, Y Terayama, T Shinohara, Y Orba, T Chuma, Y Mano, T Itoh, H Sawa, K Sakai, M Motomura, K Nagashima
NEUROPATHOLOGY, 23, 3, 230, 238, Sep. 2003, [Peer-reviewed]
English, Scientific journal

Application of laser capture microdissection to cytologic specimens for the detection of immunoglobulin heavy chain gene rearrangement in patients with malignant lymphoma
Y Orba, S Tanaka, H Nishihara, N Kawamura, T Itoh, M Shimizu, H Sawa, K Nagashima
CANCER CYTOPATHOLOGY, 99, 4, 198, 204, Aug. 2003, [Peer-reviewed]
English, Scientific journal

EphA4-mediated rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells
H Ogita, S Kunimoto, Y Kamioka, H Sawa, M Masuda, N Mochizuki
CIRCULATION RESEARCH, 93, 1, 23, 31, Jul. 2003, [Peer-reviewed]
English, Scientific journal

Human topoisomerase I promotes HIV-1 proviral DNA synthesis: Implications for the species specificity and cellular tropism of HIV-1 infection
Y Shoya, K Tokunaga, H Sawa, M Maeda, T Ueno, T Yoshikawa, H Hasegawa, T Sata, T Kurata, WW Hall, BR Cullen, H Takahashi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 100, 14, 8442, 8447, Jul. 2003, [Peer-reviewed]
English, Scientific journal

EphA4-mediated rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells
H Ogita, S Kunimoto, Y Kamioka, H Sawa, M Masuda, N Mochizuki
CIRCULATION RESEARCH, 93, 1, 23, 31, Jul. 2003
English, Scientific journal

Human topoisomerase I promotes HIV-1 proviral DNA synthesis: Implications for the species specificity and cellular tropism of HIV-1 infection
Y Shoya, K Tokunaga, H Sawa, M Maeda, T Ueno, T Yoshikawa, H Hasegawa, T Sata, T Kurata, WW Hall, BR Cullen, H Takahashi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 100, 14, 8442, 8447, Jul. 2003
English, Scientific journal

Desmoplastic malignant mesothelioma of the pleura: Autopsy reveals asbestos exposure
R Ishikawa, H Kikuchi, ML Jin, M Fujita, T Itoh, H Sawa, K Nagashima
PATHOLOGY INTERNATIONAL, 53, 6, 401, 406, Jun. 2003, [Peer-reviewed]
English, Scientific journal

Differentially expressed genes associated with cis-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and cDNA microarray
E Higuchi, N Oridata, Y Furuta, S Suzuki, H Hatakeyama, H Sawa, K Sunayashiki-Kusuzaki, K Yamazaki, Y Inuyama, S Fukuda
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 25, 3, 187, 193, Mar. 2003, [Peer-reviewed]
English, Scientific journal

Ishikawa R, Kikuchi H, Jin M, Fujita M, Itoh T, Sawa H, Nagashima K: Desmoplastic malignant mesothelioma of the pleura: Autopsy reveals asbestos exposure. Pathol Int 53: 401-406, 2003*　　　　　　　　　　　　　　　
2003

Orba Y, Nishihara H, Sawa H, Itoo T, Shimizu M, Tanaka S, Nagashima K: Application of laser capture microdissection on cytological specimens for detection of immunoglobulin heavy chain gene rearrangement of malignant lymphoma. Cancer (Cancer Cytopatho・・・　　　　　　　　　　　　　　　
2003
Orba Y, Nishihara H, Sawa H, Itoo T, Shimizu M, Tanaka S, Nagashima K: Application of laser capture microdissection on cytological specimens for detection of immunoglobulin heavy chain gene rearrangement of malignant lymphoma. Cancer (Cancer Cytopathol) 99: 198-204, 2003*

Nagashima T, Mizutani Y, Kawahara H, Maguchi S, Terayama Y, Shinohara T, Orba Y, Chuma T, Mano Y, Itoh T, Sawa H, Sakai K, Motomura M, Nagashima K. Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthen・・・　　　　　　　　　　　　　　　
2003
Nagashima T, Mizutani Y, Kawahara H, Maguchi S, Terayama Y, Shinohara T, Orba Y, Chuma T, Mano Y, Itoh T, Sawa H, Sakai K, Motomura M, Nagashima K. Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome. Neuropathology 23: 230-238, 2003*

Endo S, Okada Y, Orba Y, Nishihara H, Tanaka S, Nagashima K, Sawa H*: JC virus (JCV) agnoprotein colocalizes with tubulin. J Neurovirol 9 (Suppl 1): 10-14, 2003 (*corresponding author)*　　　　　　　　　　　　　　　
2003

Higuchi E, Oridate N, Furuta Y, Suzuki S, Hatakeyama H, Sawa H, Sunayashiki-Kusazaki K, Yamazaki-k, Inuyama-Y, Fukuda S: Differentially expressed genes associated with cis-diammeinedichloroplatinum (II) resistance in head and neck cancer using differen・・・　　　　　　　　　　　　　　　
2003
Higuchi E, Oridate N, Furuta Y, Suzuki S, Hatakeyama H, Sawa H, Sunayashiki-Kusazaki K, Yamazaki-k, Inuyama-Y, Fukuda S: Differentially expressed genes associated with cis-diammeinedichloroplatinum (II) resistance in head and neck cancer using differential display and cDNA microarray. Head Neck 25:187-93, 2003.*

Ricciardiello L, Baglioni M, Giovannini C, Pariali M, Cenacchi G, Ripalti A, Landini MP, Sawa H, Nagashima K, Frisque RJ, Goel A, Boland CR, Tognon M, Roda E, Bazzoli F: Induction of Chromosomal Instability in Colonic Cells by the Human Polyomavirus JC・・・　　　　　　　　　　　　　　　
2003
Ricciardiello L, Baglioni M, Giovannini C, Pariali M, Cenacchi G, Ripalti A, Landini MP, Sawa H, Nagashima K, Frisque RJ, Goel A, Boland CR, Tognon M, Roda E, Bazzoli F: Induction of Chromosomal Instability in Colonic Cells by the Human Polyomavirus JC Virus. Cancer Res 63:7256-62, 2003*

Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Marukawa K, Iwasaki Y, Nagashima K: Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas. J Neuropathol Exp Neurol 62: 1052-1059, 2003*　　　　　　　　　　　　　　　
2003

Yamamoto S, Furukawa H, Kitamoto T, Takamaru Y, Morita N, Yasuda M, Okada Y, Sawa H, Nagashima K: An atypical form of sporadic panencephalopathic Cleutzfeldt-Jakob disease in Japan. Neuropathol Appl Neurobiol 29: 77-80, 2003*　　　　　　　　　　　　　　　
2003

Teramoto T, Kaneko H, Futano M, Sawa H, Nagashima K, Hirose Y, Kondo N: Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia. Scand J Infect Dis 35: 910-911, 2003*　　　　　　　　　　　　　　　
2003

Mechanism of white matter damage caused by virus infection
S Semba, H Sawa, K Nagashima
ADVANCES IN BRAIN RESEARCH: CEREBROVASCULAR DISORDERS AND NEURODEGENERATION, 1251, 139, 147, 2003, [Peer-reviewed]
English, International conference proceedings

JC virus agnoprotein colocalizes with tubulin
S Endo, Y Okada, Y Orba, H Nishibara, S Tanaka, K Nagashima, H Sawa
JOURNAL OF NEUROVIROLOGY, 9, 10, 14, 2003, [Peer-reviewed]
English, Scientific journal

DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines
H Nishihara, M Maeda, A Oda, M Tsuda, H Sawa, K Nagashima, S Tanaka
BLOOD, 100, 12, 3968, 3974, Dec. 2002, [Peer-reviewed]
English, Scientific journal

Oligosaccharides as receptors for JC virus
R Komagome, H Sawa, T Suzuki, Y Suzuki, S Tanaka, WJ Atwood, K Nagashima
JOURNAL OF VIROLOGY, 76, 24, 12992, 13000, Dec. 2002, [Peer-reviewed]
English, Scientific journal

Processing of the HTLV-II envelope precursor glycoprotein gp63 by furin is essential for cell fusion activity
H Hasegawa, M Tatsumi, K Ogawa-Goto, H Takahashi, A Kojima, T Iwasaki, T Kurata, T Sata, T Takeuchi, N Sheehy, H Sawa, K Nagashima, WW Hall
AIDS RESEARCH AND HUMAN RETROVIRUSES, 18, 17, 1253, 1260, Nov. 2002, [Peer-reviewed]
English, Scientific journal

Distribution of extracellular matrix tenascin-X in sciatic nerves
K Matsumoto, H Sawa, M Sato, Y Orba, K Nagashima, H Ariga
ACTA NEUROPATHOLOGICA, 104, 5, 448, 454, Nov. 2002, [Peer-reviewed]
English, Scientific journal

Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription
H Takai, K Naka, Y Okada, M Watanabe, N Harada, S Saito, CW Anderson, E Appella, M Nakanishi, H Suzuki, K Nagashima, H Sawa, K Ikeda, N Motoyama
EMBO JOURNAL, 21, 19, 5195, 5205, Oct. 2002, [Peer-reviewed]
English, Scientific journal

Drug-induced Long-QT syndrome associated with a subclinical SCN5A mutation
N Makita, M Horie, T Nakamura, T Ai, K Sasaki, H Yokoi, M Sakurai, Sakuma, I, H Otani, H Sawa, A Kitabatake
CIRCULATION, 106, 10, 1269, 1274, Sep. 2002, [Peer-reviewed]
English, Scientific journal

Binding and dissociation of human topoisomerase I with hairpin-loop RNAs: implications for the regulation of HIV-1 replication
H Takahashi, H Sawa, H Hasegawa, T Sata, WW Hall, T Kurata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 297, 3, 593, 599, Sep. 2002, [Peer-reviewed]
English, Scientific journal

Expression of JC virus agnoprotein in progressive multifocal leukoencephalopathy brain
Y Okada, H Sawa, S Endo, Y Orba, T Umemura, H Nishihara, AC Stan, S Tanaka, H Takahashi, K Nagashima
ACTA NEUROPATHOLOGICA, 104, 2, 130, 136, Aug. 2002, [Peer-reviewed]
English, Scientific journal

DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription
H Nishihara, M Maeda, M Tsuda, Y Makino, H Sawa, K Nagashima, S Tanaka
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 296, 3, 716, 720, Aug. 2002, [Peer-reviewed]
English, Scientific journal

Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers
H Nishihara, S Tanaka, M Tsuda, S Oikawa, M Maeda, M Shimizu, H Shinomiya, A Tanigami, H Sawa, K Nagashima
CANCER LETTERS, 180, 1, 55, 61, Jun. 2002, [Peer-reviewed]
English, Scientific journal

Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus type 1
H Takahashi, H Sawa, H Hasegawa, Y Shoya, T Sata, WW Hall, K Nagashima, T Kurata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 294, 2, 509, 517, Jun. 2002, [Peer-reviewed]
English, Scientific journal

Reconstitution of cleavage of human immunodeficiency virus type-1 (HIV-1) RNAs
H Takahashi, H Sawa, H Hasegawa, T Sata, WW Hall, K Nagashima, T Kurata
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 293, 3, 1084, 1091, May 2002, [Peer-reviewed]
English, Scientific journal

Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase lambda-deficient mice: Possible implication for the pathogenesis of immotile cilia syndrome
Y Kobayashi, M Watanabe, Y Okada, H Sawa, H Takai, M Nakanishi, Y Kawase, H Suzuki, K Nagashima, K Ikeda, N Motoyama
MOLECULAR AND CELLULAR BIOLOGY, 22, 8, 2769, 2776, Apr. 2002, [Peer-reviewed]
English, Scientific journal

Advanced glycation end products induce angiogenesis in vivo
T Okamoto, S Tanaka, AC Stan, T Koike, M Kase, Z Makita, H Sawa, K Nagashima
MICROVASCULAR RESEARCH, 63, 2, 186, 195, Mar. 2002, [Peer-reviewed]
English, Scientific journal

Signaling adaptor protein v-Crk activates Rho and regulates cell motility in 3Y1 rat fibroblast cell line
M Tsuda, S Tanaka, H Sawa, H Hanafusa, K Nagashima
CELL GROWTH & DIFFERENTIATION, 13, 3, 131, 139, Mar. 2002, [Peer-reviewed]
English, Scientific journal

Molecular neuropathology of JC virus
Yasuko Orba, Hirofumi Sawa, Kazuo Nagashima
Brain and Nerve, 54, 2, 101, 109, 2, 2002, [Peer-reviewed]
Japanese

Tsuda, M., Tanaka, S., Sawa, H., Hanafusa, H., Nagashima: Signalling adaptor protein v-Crk activates Rho and regulates cell motility in 3Y1 rat fibroblast cell line. Cell Growth Diff 13: 131-139, 2002*　　　　　　　　　　　　　　　
2002

Makita N, Horie M, Nakamura T, Ai T, Otani H, Sawa H, Kitabatake A: Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation 106: 1269-1274, 2002*　　　　　　　　　　　　　　　
2002

Hasegawa H, Tatsumi M, Ogawa-Goto K, Takahashi H, Iwasaki T, Kurata T, Sata T, Takeuchi T, Sheehy N, Sawa H, Nagashima K, Hall WW: Processing of the HTLV-II envelope precursor glycoprotein, gp63 by furin is essential for cell fusion activity. AIDS Res・・・　　　　　　　　　　　　　　　
2002
Hasegawa H, Tatsumi M, Ogawa-Goto K, Takahashi H, Iwasaki T, Kurata T, Sata T, Takeuchi T, Sheehy N, Sawa H, Nagashima K, Hall WW: Processing of the HTLV-II envelope precursor glycoprotein, gp63 by furin is essential for cell fusion activity. AIDS Res Hum Retroviruses 18: 1253-1260, 2002*

Takai H, Naka K, Okada Y, Watanabe M, Harada N, Saito S, Anderson CW, Appella E, Nakanishi M, Suzuki H, Nagashima K, Sawa H, Ikeda K, Motoyama N: Chk2-deficient mice exhibit increased resistance to ionizing radiation and defective p53-mediated transcri・・・　　　　　　　　　　　　　　　
2002
Takai H, Naka K, Okada Y, Watanabe M, Harada N, Saito S, Anderson CW, Appella E, Nakanishi M, Suzuki H, Nagashima K, Sawa H, Ikeda K, Motoyama N: Chk2-deficient mice exhibit increased resistance to ionizing radiation and defective p53-mediated transcription. EMBO J 21: 5195-5205, 2002*

Takahashi H, Sawa H, Hasegawa H, Shoya Y, Sata T, Hall WW, Nagashima K, Kurata T: Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus type-1 (HIV-1). Biochem Biophys Res Commun 294: 509-517, 2002　　　　　　　　　　　　　　　
2002

Hasegawa H, Tatsumi M, Ogawa-Goto K, Takahashi H, Iwasaki T, Kurata T, Sata T, Takeuchi T, Sheehy N, Sawa H, Nagashima K, Hall WW: "Processing of the HTLV-II envelope precursor glycoprotein, gp63 by furin is essential for cell fusion activity." AIDS R・・・　　　　　　　　　　　　　　　
2002
Hasegawa H, Tatsumi M, Ogawa-Goto K, Takahashi H, Iwasaki T, Kurata T, Sata T, Takeuchi T, Sheehy N, Sawa H, Nagashima K, Hall WW: "Processing of the HTLV-II envelope precursor glycoprotein, gp63 by furin is essential for cell fusion activity." AIDS Res Hum Retroviruses 18: 1253-1260, 2002*

Nishihara H, Tanaka S, Tsuda M., Oikawa S, Maeda M, Shimizu M, Shimoyama H, Tanigami A, Sawa H, Nagashima K: "Molecular and immunohistochemical analysis of adaptor protein Crk in human cancers." Cancer Lett 180, 55-61, 2002*　　　　　　　　　　　　　　　
2002

Matsumoto K, Sawa H, Sato M, Orba Y, Nagashima K, Ariga H: "Distribution of extracellular matrix tenascin-X in sciatic nerves." Acta Neuropathol 104: 448-454, 2002*　　　　　　　　　　　　　　　
2002

Tsuda, M., Tanaka, S., Sawa, H., Hanafusa, H., and Nagashima: "Signalling adaptor protein v-Crk activates Rho and regulates cell motility in 3Y1 rat fibroblast cell line." Cell Growth Diff 13: 131-139, 2002*　　　　　　　　　　　　　　　
2002

Takahashi H, Sawa H, Hasegawa H, Sata T, Hall WW, Nagashima K, Kurata T: "Reconstitution of cleavage of human immunodeficiency virus type-1 (HIV-1) RNAs." Biochem Biophys Res Commun 293: 1084-1091, 2002*　　　　　　　　　　　　　　　
2002

Yoshida H, Okada Y, Kinoshita N, Hara H, Sasaki M, Sawa H, Nagashima K, Mak TW, Motoyama N: "Differential requirement for Apaf1 and Bcl-XL in the regulation of programmed cell death during development." Cell Death Differ 9: 1273-1276, 2002*　　　　　　　　　　　　　　　
2002

Takahashi H, Sawa H, Hasegawa H, Sata T, Hall WW, Kurata T: "Binding and dissociation of human topoisomerase I with hair-pin loop RNAs: implications for the regulation of HIV-1 replication." Biochem Biophys Res Commun 297: 593-599, 2002*　　　　　　　　　　　　　　　
2002

Komagome R, Sawa H*, Suzuki T, Suzuki Y, Tanaka S, Atwood WJ, Nagashima K: "Oligosaccharides as receptors for JC virus." J Virol 76: 12992-13000, 2002 (* corresponding author)*　　　　　　　　　　　　　　　
2002

Nishihara H, Maeda M, Oda A, Tsuda M, Sawa H, Tanaka S, and Nagashima K: "DOCK2 associates with CrkL and regulates Rac1 in hematopoietic cells." Blood 100: 3968-3974, 2002*　　　　　　　　　　　　　　　
2002

Takai H, Naka K, Okada Y, Watanabe M, Harada N, Saito S, Anderson CW, Appella E, Nakanishi M, Suzuki H, Nagashima K, Sawa H, Ikeda K, Motoyama N: "Chk2-deficient mice exhibit increased resistance to ionizing radiation and defective p53-mediated transcr・・・　　　　　　　　　　　　　　　
2002
Takai H, Naka K, Okada Y, Watanabe M, Harada N, Saito S, Anderson CW, Appella E, Nakanishi M, Suzuki H, Nagashima K, Sawa H, Ikeda K, Motoyama N: "Chk2-deficient mice exhibit increased resistance to ionizing radiation and defective p53-mediated transcription." EMBO J 21: 5195-5205, 2002*

Nishihara H, Maeda M, Tsuda M, Makino Y, Sawa H, Nagashima K, Tanaka S: "DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription." Biochem Biophys Res Commun 296: 716-720, 2002*　　　　　　　　　　　　　　　
2002

Okada Y, Sawa H, Endo S, Orba Y, Umemura T, Nishihara H, Stan AC, Tanaka S, Nagashima K. "Expression of JC virus (JCV) agnoprotein in progressive multifocal leukoencephalopathy (PML) brain." Acta Neuropathol 104: 130-136, 2002*　　　　　　　　　　　　　　　
2002

Coronary reperfusion following ischemia - Different expression of bcl-2 and bax proteins, and cardiomyocyte apoptosis
ZL Xie, T Koyama, J Suzuki, Y Fujii, H Togashi, H Sawa, K Nagashima
JAPANESE HEART JOURNAL, 42, 6, 759, 770, Nov. 2001, [Peer-reviewed]
English, Scientific journal

Developmental and functional analyses of CD8+ NK1.1+ T cells in class-I-restricted TCR transgenic mice
Ryuichiro Ohwatari, Kazuya Iwabuchi, Chikako Iwabuchi, Taiki Morohashi, Hirofumi Sawa, Kyoji Hioki, Kimio Kobayashi, Satoshi Fukuda, Yukio Inuyama, Kazunori Onoé
Cellular Immunology, 213, 1, 24, 33, Academic Press Inc., 10 Oct. 2001, [Peer-reviewed]
English, Scientific journal

Adult T-cell lymphoma involving the leptomeninges associated with a spinal cord schwannoma
T Nagashima, M Mori, M Fujimoto, M Nunomura, Y Sakurai, Y Okada, T Itoh, H Sawa, AC Stan, K Nagashima
NEUROPATHOLOGY, 21, 3, 229, 235, Sep. 2001, [Peer-reviewed]
English, Scientific journal

Distribution and function of JCV agnoprotein
Y Okada, S Endo, H Takahashi, H Sawa, T Umemura, K Nagashima
JOURNAL OF NEUROVIROLOGY, 7, 4, 302, 306, Aug. 2001, [Peer-reviewed]
English, Scientific journal

Quantitation of varicella-zoster virus DNA in patients with Ramsay Hunt syndrome and zoster sine herpete
Y Furuta, F Ohtani, H Sawa, S Fukuda, Y Inuyama
JOURNAL OF CLINICAL MICROBIOLOGY, 39, 8, 2856, 2859, Aug. 2001, [Peer-reviewed]
English, Scientific journal

Angiotensin-converting enzyme inhibition attenuates hypofibrinolysis and reduces cardiac perivascular fibrosis in genetically obese diabetic
AKMT Zaman, S Fujii, H Sawa, D Goto, N Ishimori, K Watano, T Kaneko, T Furumoto, T Sugawara, Sakuma, I, A Kitabatake, BE Sobel
CIRCULATION, 103, 25, 3123, 3128, Jun. 2001, [Peer-reviewed]
English, Scientific journal

Analysis of transforming activity of human synovial sarcoma-associated chimeric protein SYT-SSX1 bound to chromatin remodeling factor hBRM/hSNF2α
Makoto Nagai, Shinya Tanaka, Masumi Tsuda, Shuichi Endo, Hiroyuki Kato, Hiroshi Sonobe, Akio Minami, Hiroaki Hiraga, Hiroshi Nishihara, Hirofumi Sawa, Kazuo Nagashima
Proceedings of the National Academy of Sciences of the United States of America, 98, 7, 3843, 3848, 27 Mar. 2001
English, Scientific journal

Analysis of transforming activity of human synovial sarcoma-associated chimeric protein SYT-SSX1 bound to chromatin remodeling factor hBRM/hSNF2 alpha
M Nagai, S Tanaka, M Tsuda, S Endo, H Kato, H Sonobe, A Minami, H Hiraga, H Nishihara, H Sawa, K Nagashima
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 98, 7, 3843, 3848, Mar. 2001, [Peer-reviewed]
English, Scientific journal

Okada Y, Endo S, Takahashi H, Sawa H, Umemura T, Nagashima K: "Distribution and function of JCV agnoprotein." J Neurovirol 7: 302-306, 2001　　　　　　　　　　　　　　　
2001

Suzuki S, Sawa H*, Komagome R, Orba Y, Yamada M, Okada Y, Ishida Y, Nishihara H, Tanaka S, Nagashima K: "Broad distribution of the JC virus receptor contrasts with a marked cellular restriction of virus replication." Virology 286: 100-112, 2001 (* cor・・・　　　　　　　　　　　　　　　
2001
Suzuki S, Sawa H*, Komagome R, Orba Y, Yamada M, Okada Y, Ishida Y, Nishihara H, Tanaka S, Nagashima K: "Broad distribution of the JC virus receptor contrasts with a marked cellular restriction of virus replication." Virology 286: 100-112, 2001 (* corresponding author)*

Shirane M, Sawa H, Kobayashi Y, Nakano T, Shinkai Y, Nagashima K, and Negishi I. "Deficiency of phospholipase C-1 impares renal development and hematopoiesis." Development 128: 5173-5180, 2001*　　　　　　　　　　　　　　　
2001

Okamoto T, Tanaka S, Stan AC., Koike T, Kase, Makita Z, Sawa H, Ngashima K: "Advanced glycation end products induce angiogenesis in vivo." Microvascular Research 63: 186-195, 2002*　　　　　　　　　　　　　　　
2001

Tanaka S, Katano H, Tsukamoto K, Jin M, Oikawa S, Nishihara H, Sawa H, Sawada K, Shimizu M, Sata T, Fujioka Y, Nagashima K. "HHV8-negative primary effusion lymphoma of the peritoneal cavity presenting with a distinct immunohistochemical phenotype." Pa・・・　　　　　　　　　　　　　　　
2001
Tanaka S, Katano H, Tsukamoto K, Jin M, Oikawa S, Nishihara H, Sawa H, Sawada K, Shimizu M, Sata T, Fujioka Y, Nagashima K. "HHV8-negative primary effusion lymphoma of the peritoneal cavity presenting with a distinct immunohistochemical phenotype." Pathol Int 51: 293-300, 2001*

Ohwatari R, Iwabuchi K, Iwabuchi C, Morohashi T, Sawa H, Hioki K, Kobayash i K, Fukuda S, Inuyama Y, and Onoe K. "Developmental and functional analyses of CD8+ NK1.1+ T cells in the class I restricted TCR transgenic mice." Cell Immunol. 213: 24-33, 2001*　　　　　　　　　　　　　　　
2001

Nagashima T, Mori M, Fujimoto M, Nunomura M, Sakurai Y, Okada Y, Itoh T, Sawa H, Stan AC, Nagashima K: "Adult T-cell lymphoma involving the leptomeninges associated with a spinal cord schwannoma." Neuropathology 21, 229-235, 2001　　　　　　　　　　　　　　　
2001

Furuta Y, Ohtani F, Sawa H, Fukuda S, Inuyama Y: "Quantitation of varicella-zoster virus DNA in patients with Ramsay Hunt syndrome and Zoster Sine Herpete." J Clin Microbiol 39: 2856-2859, 2001.*　　　　　　　　　　　　　　　
2001

Kamimura E, UenoY, Tanaka S, Sawa H, Yoshioka M, Ueno K, Ishikawa R, Inoue T, Li X, Koyama T, Nagashima K: "New rat model for attention deficit hyperactive disorder (ADHD)." Comp Med 51: 245-251, 2001*　　　　　　　　　　　　　　　
2001

Ohnishi J, Ohnishi E, Hirano W, Nakane D, Matsui H, Kimura A, Sawa H, Nakayama K, Shibuya H, Nagashima K, Takahashi T: Cloning and characterization of a rat ortholog of MMP-23 (matrix metalloproteinase-23), a unique type of membrane-anchored matrix met・・・　　　　　　　　　　　　　　　
2001
Ohnishi J, Ohnishi E, Hirano W, Nakane D, Matsui H, Kimura A, Sawa H, Nakayama K, Shibuya H, Nagashima K, Takahashi T: Cloning and characterization of a rat ortholog of MMP-23 (matrix metalloproteinase-23), a unique type of membrane-anchored matrix metalloproteinase and conditioned switching of its expression during the ovarian follicular development. Mol Endocrinol 15, 747-764, 2001*

Hayashi H, Endo S, Suzuki S, Tanaka S, Sawa H, Ozaki Y, Sawamura Y, Nagashima K: "JC virus large T protein transforms rodent cells but is not involved in human medulloblastoma." Neuropathology 21: 129-137, 2001*　　　　　　　　　　　　　　　
2001

Xie Z, Koyama T, Suzuki J, Fujii Y, Togashi H, Sawa H, Nagashima K: Coronary reperfusion following ischemia. Different expression of Bcl-2 and Bax proteins, and cardiomyocyte apoptosis. Jpn Heart J 42: 759-770, 2001*　　　　　　　　　　　　　　　
2001

Impression of the 3rd International Symposium of Neurovirology (ISNV) Meeting 2000
Sawa Hirofumi
Uirusu, 51, 1, 113, 118, The Japanese Society for Virology, 2001
Japanese

Cloning and characterization of a rat ortholog of MMP-23 (matrix metalloproteinase-23), a unique type of membrane-anchored matrix metalloproteinase and conditioned switching of its expression during the ovarian follicular development
J. Ohnishi, E. Ohnishi, M. Jin, W. Hirano, D. Nakane, H. Matsui, A. Kimura, H. Sawa, K. Nakayama, H. Shibuya, K. Nagashima, T. Takahashi
Molecular Endocrinology, 15, 5, 747, 764, Endocrine Society, 2001, [Peer-reviewed]
English, Scientific journal

Deficiency of phospholipase C-γ1 impairs renal development and hematopoiesis
Masatoshi Shirane, Hirofumi Sawa, Yoshiyasu Kobayashi, Toru Nakano, Kenji Kitajima, Yoichi Shinkai, Kazuo Nagashima, Izumi Negishi
Development, 128, 24, 5173, 5180, 2001, [Peer-reviewed]
English, Scientific journal

New rat model for attention deficit hyperactive disorder (ADHD)
E. Kamimura, Y. Ueno, S. Tanaka, H. Sawa, M. Yoshioka, K. I. Ueno, T. Inoue, X. Li, T. Koyama, R. Ishikawa, K. Nagashima
Comparative Medicine, 51, 3, 245, 251, 2001, [Peer-reviewed]
English, Scientific journal

Infection with JC virus and possible dysplastic ganglion-like transformation of the cerebral cortical neurons in a case of progressive multifocal leukoencephalopathy
M Shintaku, R Matsumoto, H Sawa, K Nagashima
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 59, 10, 921, 929, Oct. 2000
English, Scientific journal

CalDAG-GEFIII activation of Ras, R-Ras, and Rap1
S. Yamashita, N. Mochizuki, Y. Ohba, M. Tobiume, Y. Okada, H. Sawa, K. Nagashima, M. Matsuda
Journal of Biological Chemistry, 275, 33, 25488, 25493, 18 Aug. 2000
English, Scientific journal

CalDAG-GEFIII activation of Ras, R-Ras, and Rap1
S Yamashita, N Mochizuki, Y Ohba, M Tobiume, Y Okada, H Sawa, K Nagashima, M Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 33, 25488, 25493, Aug. 2000, [Peer-reviewed]
English, Scientific journal

Transcriptional activation of JC virus by human T-lymphotropic virus type I tax protein in human neuronal cell lines
Y Okada, H Sawa, S Tanaka, A Takada, S Suzuki, H Hasegawa, T Umemura, J Fujisawa, Y Tanaka, WW Hall, K Nagashima
JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 22, 17016, 17023, Jun. 2000, [Peer-reviewed]
English, Scientific journal

Sato-Matsumura KC, Matsumura T, Nakamura H, Sawa H, Nagashima K, Koizumi H: Membranous expression of annexin I is enhanced by calcium and TPA in cultured human keratinocytes. Arch Dermatol Res 292, 496-499, 2000*　　　　　　　　　　　　　　　
2000

Hiroi Y, Chen R, Sawa H, Hosoda T, Kudoh S, Kobayashi Y, Aburatani H, Nagashima K, Nagai R, Yazaki Y, Medof ME, Komuro I: Cloning of murine glycosyl phosphatidylinositol anchor attachment protein, GPAA1. Am J Physiol Cell Physiol 279, C205-C212, 2000*　　　　　　　　　　　　　　　
2000

Xie Z, Koyama T, Abe K, Fujii Y, Sawa H, Nagashima K: Upregulation of p53 protein in rat heart subjected to a transient occlusion of the coronary artery followed by reperfusion. Jpn J Physiol 50: 159-162, 2000*　　　　　　　　　　　　　　　
2000

Membrane expression of annexin I is enhanced by calcium and TPA in cultured human keratinocytes
K. C. Sato-Matsumura, T. Matsumura, H. Nakamura, H. Sawa, K. Nagashima, H. Koizumi
Archives of Dermatological Research, 292, 10, 496, 499, 2000, [Peer-reviewed]
English, Scientific journal

Upregulation of p53 protein in rat heart subjected to a transient occlusion of the coronary artery followed by reperfusion
Zhonglin Xie, Tomiyasu Koyama, Kazuhiro Abe, Yukiko Fujii, Hirofumi Sawa, Kazuo Nagashima
Japanese Journal of Physiology, 50, 1, 159, 162, The Physiological Society of Japan, 2000, [Peer-reviewed]
English, Scientific journal

Cloning of murine glycosyl phosphatidylinositol anchor attachment protein, GPAA1
Y. Hiroi, R. Chen, H. Sawa, T. Hosoda, S. Kudoh, Y. Kobayashi, H. Aburatani, K. Nagashima, R. Nagai, Y. Yazaki, M. E. Medof, I. Komuro
American Journal of Physiology - Cell Physiology, 279, 1, C205, C212, 2000, [Peer-reviewed]
English, Scientific journal

Melanotic peritoneal sarcomatosis originating from clear cell sarcoma
Y Ohba, H Suzuki, H Hiraga, T Ito, H Sawa, M Nagai, S Satoh, H Iwaki, K Nagashima
PATHOLOGY INTERNATIONAL, 49, 7, 653, 657, Jul. 1999, [Peer-reviewed]
English, Scientific journal

Pertussis toxin-sensitive signal controls the trafficking of thymocytes across the corticomedullary junction in the thymus
Gen Suzuki, Hirofumi Sawa, Yoshiyasu Kobayashi, Yukiko Nakata, Ken-Ichi Nakagawa, Akiko Uzawa, Hisako Sakiyama, Shizuko Kakinuma, Kazuya Iwabuchi, Kazuo Nagashima
Journal of Immunology, 162, 10, 5981, 5985, 15 May 1999, [Peer-reviewed]
English, Scientific journal

JCウイルスcapsid proteinの機能的領域に対する抗体を用いた免疫組織学的検索と感染抑制実験　　　　　　　　　　　　　　　
西原 広史, 小林 希, 佐藤 真実, 宍戸 由紀子, 岡田 由紀, 田中 伸哉, 澤 洋文, 古林 与志安, 長嶋 和郎
日本病理学会会誌, 88, 1, 333, 333, (一社)日本病理学会, Mar. 1999, [Peer-reviewed]
Japanese

Pertussis toxin-sensitive signal controls the trafficking of′ thymocytes across the corticomedullary junction in the′ thymus.
Suzuki G., Sawa H., Kobayashi Y., Nakata Y., Nakagawa ′ K., Uzawa A., Sakiyama H., Kakinuma S., Iwabuchi K., ′ Nagashima K.
Collected papers from Institute for Genetic Medicine Hokkaido University, 1, 276, 280, Hokkaido University, 1999
English, Suzuki G, Sawa H, Kobayashi Y, Nakata Y, Nakagawa Ki, Uzawa A, Sakiyama H, Kakinuma S, Iwabuchi K, Nagashima K: Pertussis toxin-sensitive signal controls the trafficking of thymocytes across corticomedullary junction in the thymus. J Immunol 162: 5981-5985, 1999*

Ohba Y, Suzuki H, Hiraga H, Ito T, Sawa H, Nagai M, Satoh S, Iwaki H, Nagashima K. Melanotic peritoneal sarcomatosis originating from clear cell sarcoma. Pathol Int 49: 653-657, 1999*　　　　　　　　　　　　　　　
1999

Calbindin D immunoreactivity and chronic lesions of rat cerebella in methylmercury chloride intoxication
Y Kobayashi, H Sawa, M Watanabe, H Furuoka, T Matsui, K Nagashima
NEUROPATHOLOGY, 18, 4, 402, 407, Dec. 1998, [Peer-reviewed]
English, Scientific journal

CXCR4の発現と胸腺細胞分化　　　　　　　　　　　　　　　
中川 憲一, 中田 有紀子, 鵜沢 玲子, 澤 洋文, 古林 与志安, 長嶋 和郎, 岩渕 和也, 鈴木 元
日本臨床免疫学会会誌, 26回抄録集, 266, 266, 日本臨床免疫学会, Oct. 1998, [Peer-reviewed]
Japanese

Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor type-1 (PAI-1) gene by proinsulin and insulin in vivo
TK Nordt, H Sawa, S Fujii, C Bode, BE Sobel
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 30, 8, 1535, 1543, Aug. 1998
English, Scientific journal

Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain reaction: Analyses of 84 soft tissue and bone tumors
H Hiraga, T Nojima, S Abe, H Sawa, K Yamashiro, S Yamawaki, K Kaneda, K Nagashima
DIAGNOSTIC MOLECULAR PATHOLOGY, 7, 2, 102, 110, Apr. 1998, [Peer-reviewed]
English, Scientific journal

Hiraga H, Nojima T, Abe S, Sawa H, Yamashiro K, Yamawaki S, Kaneda K, Nagashima K: Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain reaction: analyses of 84 soft tissue and bone tumors. Diagn Mol Pathol 7: 102-110, (1998)*　　　　　　　　　　　　　　　
1998

Sasaki H, Kojima H, Yabe I, Tashiro K, Hamada T, Sawa H, Hiraga H, Nagashima K: Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6). Acta Neuropathology (Berl) 95: 199-204, 1998*　　　　　　　　　　　　　　　
1998

Kobayashi Y, Sawa H, Akagi H, Itakura C, Fujioka Y, Nagashima K: Distributional pattern of apoptotic cells in rat cerebellar vermis experimentally induced by methylmercury intoxication. Neuropathology 18: 33-37, 1998*　　　　　　　　　　　　　　　
1998

Kobayashi Y, Sawa H, Watanabe M, Furuoka H, Matsui T, Nagashima K: Calbindin D immunoreactivity and chronic lesions of rat cerebella in methylmercury chrolide intoxication. Neuropathology 18: 402-407, 1998*　　　　　　　　　　　　　　　
1998

Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6)
Hidenao Sasaki, Hideaki Kojima, Ichiro Yabe, Kunio Tashiro, Takeshi Hamada, Hirofumi Sawa, Hiroaki Hiraga, Kazuo Nagashima
Acta Neuropathologica, 95, 2, 199, 204, 1998, [Peer-reviewed]
English, Scientific journal

Nordt TK, Sawa H, Fujii S, Sobel BE: Hyperinsulinemia increases plasma activity of PAI-1 in vivo independently of an acute phase reaction. Fibrinolysis Proteolysis 11 : 51-54, 1997　　　　　　　　　　　　　　　
1997

Takahashi HR, Sawa H, Takada A, Kitabatake A, Nagashima K: Expression of beta-amyloid precursor protein mRNAs in the vascular smooth muscle cell of human brain. Neuropathology 17: 11-14, 1997*　　　　　　　　　　　　　　　
1997

Localization of annexin I (lipocortin I, p35) mRNA in normal and diseased human skin by in situ hybridization
KC SatoMatsumura, H Koizumi, T Matsumura, A Ohkawara, T Takasu, Y Furuta, H Sawa, K Nagashima
ARCHIVES OF DERMATOLOGICAL RESEARCH, 288, 10, 565, 569, Sep. 1996, [Peer-reviewed]
English, Scientific journal

Shinohara K, Shinohara T, Mochizuki N, Mochizuki Y, Sawa H, Kohya T, Fujita M, Fujioka Y, Kitabatake A, Nagashima K: Expression of vascular endothelial growth factor associated with human myocardial infarction. Heart Vessels 11: 113-122, 1996*　　　　　　　　　　　　　　　
1996

Matsumura SCK, Koizumi H, Matsumura T, Ohkawara A, Takasu T, Furuta Y, Sawa H, Nagashima K: Localization of annexin I (lipocortin I, p35) mRNA in normal and diseased human skin by in situ hybridization. Arch Dermatol Res 288:565-569, 1996*
1996

Takahashi HR, Sawa H, Kuroda S, Saito H, Fujita M, Fujioka Y, Fukatsu R, Nagashima K: Pathologic processes leading to cerebral hemorrhage in amyloid angiopathy. Neuropathology 16: 99-105, 1996*　　　　　　　　　　　　　　　
1996

Okada H, Kawaguchi H, Kudo T, Sawa H, Okamoto H, Watanabe S, Urasawa K, Murakami T, Kitabatake A: Alteration of extracellular matrix in dilated cardiomyopathic hamster heart. Mol Cell Biochem 156: 9-15, 1996*　　　　　　　　　　　　　　　
1996

Sawa H, Lundgren CH, Brown SL, Fujii S: Dependence of human vascular cell surface proteolysis on expression of the urokinase receptor. J Thromb Thromboly 3: 331-336, 1996*　　　　　　　　　　　　　　　
1996

Alteration of extracellular matrix in dilated cardiomyopathic hamster heart
Hitoshi Okada, Hideaki Kawaguchi, Toshiyuki Kudo, Hirofumi Sawa, Hiroshi Okamoto, Shouzi Watanabe, Kazushi Urasawa, Takeshi Murakami, Akira Kitabatake
Molecular and Cellular Biochemistry, 156, 1, 9, 15, Kluwer Academic Publishers, 1996, [Peer-reviewed]
English, Scientific journal

EXPRESSION OF INTERCELLULAR AND VASCULAR CELL-ADHESION MOLECULES AND CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS IN HUMAN LUNGS - LACK OF INFLUENCE BY CONDITIONS OF ORGAN PRESERVATION
S HASEGAWA, JH RITTER, GA PATTERSON, DM OCKNER, H SAWA, T MOHANAKUMAR, JD COOPER, MR WICK
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 14, 5, 897, 905, Sep. 1995, [Peer-reviewed]
English, Scientific journal

Mochizuki EY, Mochizuki N, Sawa H, Takada A, Okamoto H, Kawaguchi H, Nagashima K, Kitabatake A: Expression of renin and angiotensin converting enzyme in human hearts. Heart Vessels 10: 285-293, 1995*　　　　　　　　　　　　　　　
1995

Nordt TK, Sawa H, Fujii S, Sobel BE: Induction of plasminogen activator inhibitor type-1 (PAI-1) by proinsulin and insulin in vivo. Circulation 91: 764-770, 1995*　　　　　　　　　　　　　　　
1995

Motoyama N, Wang F, Roth KA, Sawa H, Nakayama Ki, Nakayama K, Negishi I, Senju S, Zhang Q, Fujii S, Loh DY: Massiva cell death of post-mitotic immature lymphocytes in Bcl-x-deficient mice. Science 267: 1506-1510, 1995*　　　　　　　　　　　　　　　
1995

Expression of renin and angiotensin-converting enzyme in human hearts
Y EndoMochizuki, N Mochizuki, H Sawa, A Takada, H Okamoto, H Kawaguchi, K Nagashima, A Kitabatake
HEART AND VESSELS, 10, 6, 285, 293, 1995, [Peer-reviewed]
English, Scientific journal

Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice
Noboru Motoyama, Fanping Wang, Kevin A. Roth, Hirofumi Sawa, Kei Ichi Nakayama, Keiko Nakayama, Izumi Negishi, Satoru Senju, Qing Zhang, Satoshi Fujii, Dennis Y. Loh
Science, 267, 1506, 1510, 01 Jan. 1995

INCREASED INTRAMURAL EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 AFTER BALLOON INJURY - A POTENTIAL PROGENITOR OF RESTENOSIS
H SAWA, C LUNDGREN, BE SOBEL, S FUJII
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 24, 7, 1742, 1748, Dec. 1994
English, Scientific journal

MODULATION OF EXPRESSION OF MONOCYTE/MACROPHAGE PLASMINOGEN-ACTIVATOR ACTIVITY AND ITS IMPLICATIONS FOR ATTENUATION OF VASCULOPATHY
CH LUNDGREN, H SAWA, BE SOBEL, S FUJII
CIRCULATION, 90, 4, 1927, 1934, Oct. 1994
English, Scientific journal

INHIBITION OF TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR PRODUCTION BY ANTISENSE OLIGONUCLEOTIDES IN HUMAN VASCULAR ENDOTHELIAL AND SMOOTH-MUSCLE CELLS
H SAWA, BE SOBEL, S FUJII
JOURNAL OF BIOLOGICAL CHEMISTRY, 269, 19, 14149, 14152, May 1994
English, Scientific journal

Targeted disruption of Bcl-2αβ in mice: Occurrence of gray hair, polycystic kidney disease, and lymphocytopenia
Keiko Nakayama, Kei Ichi Nakayama, Izumi Negishi, Keisuke Kuida, Hirofumi Sawa, Dennis Y. Loh
Proceedings of the National Academy of Sciences of the United States of America, 91, 3700, 3704, 26 Apr. 1994

Distribution of angiotensinogen in diseased human hearts
Hirofumi Sawa, Hideaki Kawaguchi, Naoki Mochizuki, Yuka Endo, Toshiyuki Kudo, Fumio Tokuchi, Yasunori Fijioka, Kazuo Nagashima, Akira Kitabatake
Molecular and Cellular Biochemistry, 132, 1, 15, 23, Kluwer Academic Publishers, Mar. 1994, [Peer-reviewed]
English, Scientific journal

Nakayama K, Nakayama K-i, Negishi I, Kuida K, Sawa H, Loh DY: Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair,polycystic kidney disease, and lymphocytopenia. Proc Natl Acad Sci U S A 91: 3700-3704, 1994*　　　　　　　　　　　　　　　
1994

Sawa H, Kawaguchi H, Mochizuki N, Endo Y, Kudo T, Tokuchi F, Fujioka Y, Nagashima K, Kitabatake A: Distribution of angiotensinogen in diseased human hearts. Mol Cell Biochem 132: 15-23, 1994*　　　　　　　　　　　　　　　
1994

POTENTIATION BY HYPERCHOLESTEROLEMIA OF THE INDUCTION OF AORTIC INTRAMURAL SYNTHESIS OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 BY ENDOTHELIAL INJURY
H SAWA, BE SOBEL, S FUJII
CIRCULATION RESEARCH, 73, 4, 671, 680, Oct. 1993
English, Scientific journal

Fujii S, Sawa H, Sobel BE: Inhibition of endothelial cell expression of plasminogen activator inhibitor type-1 by gemfibrozil. Thromb Haemost 70: 642-647, 1993*　　　　　　　　　　　　　　　
1993

INDUCTION OF ENDOTHELIAL-CELL EXPRESSION OF THE PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 GENE BY THROMBOSIS INVIVO
S FUJII, H SAWA, JE SAFFITZ, CL LUCORE, BE SOBEL
CIRCULATION, 86, 6, 2000, 2010, Dec. 1992
English, Scientific journal

Furuta Y, Takasu T, Asai T, Shinohara T, Sawa H, Nagashima K, Inuyama Y: Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction. Cancer 69: 353-357, 1992　　　　　　　　　　　　　　　
1992

Sawa H, Fujii S, Sobel BE: Augmented arterial wall expression of type-1 plasminogen activator inhibitor induced by thrombosis. Arterioscler Thromb 12: 1507-1515, 1992　　　　　　　　　　　　　　　
1992

Kawaguchi H, Shoki M, Sano H, Kudo T, Sawa H, Mochizuki N, Okamoto H, Endo Y, Kitabatake A: Polyphosphoinositide metabolism in hypertrophic rat heart. J Mol Cell Cardiol 24: 1003-1010, 1992*　　　　　　　　　　　　　　　
1992

Sawa H, Tokuchi F, Mochizuki N, Endo Y, Furuta Y, Shinohara T, Takada A, Kawaguchi H, Yasuda H, Nagashima K: Expression of the angiotensinogen gene and localization of its protein in the human heart. Circulation 86: 138-146, 1992　　　　　　　　　　　　　　　
1992

Shoki M, Kawaguchi H, Okamoto H, Sano H, Sawa H, Kudo T, Hirao N, Sakata Y, Yasuda H: Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart. Jpn Circ J 56:142-147, 1992*　　　　　　　　　　　　　　　
1992

Kawaguchi H, Shoki M, Sano H, Kudo T, Sawa H, Okamoto H, Sakata Y, Yasuda H: The studies of cell damaging and cell growth factors which induce cardiomyopathy. Jpn Circ J 56: 1037-1044, 1992*　　　　　　　　　　　　　　　
1992

Polyphosphoinositide metabolism in hypertrophic rat heart
Hideaki Kawaguchi, Mikako Shoki, Hitoshi Sano, Toshiyuki Kudo, Hirofumi Sawa, Naoki Mochizuki, Hiroshi Okamoto, Yuka Endo, Akira Kitabatake
Journal of Molecular and Cellular Cardiology, 24, 9, 1003, 1010, 1992, [Peer-reviewed]
English, Scientific journal

The studies of cell damaging and cell growth factors which induce cardiomyopathy
Hideaki Kawaguchi, Ikako Shoki, Hitoshi Sano, Toshiyuki Kudo, Hirofumi Sawa, Hiroshi Okamoto, Yoshihito Sakata, Hisakazu Yasuda
JAPANESE CIRCULATION JOURNAL, 56, 10, 1037, 1044, 1992, [Peer-reviewed]
English, Scientific journal

EFFECT OF ENDOTHELIN ON ANGIOTENSIN CONVERTING ENZYME-ACTIVITY IN CULTURED PULMONARY-ARTERY ENDOTHELIAL-CELLS
H KAWAGUCHI, H SAWA, H YASUDA
JOURNAL OF HYPERTENSION, 9, 2, 171, 174, Feb. 1991
English, Scientific journal

Kawaguchi H, Shoki M, Sano H, Kudo T, Sawa H, Okamoto H, Sakata Y, Yasuda H: Phospholipid metabolism in cardiomyopathic hamster heart cells. Circ Res 69: 1015-1021, 1991*　　　　　　　　　　　　　　　
1991

Mochizuki N, Sawa H, Yasuda H, Shinohara T, Nagashima K, Yamaji N, Ohnuma N, Hall WW: Distribution of atrial natriuretic peptide in the conduction system and ventricular muscles of the human heart. Virchows Arch A Pathol Anat Histopathol 418: 9-16, 1991*　　　　　　　　　　　　　　　
1991

Phospholipid metabolism in cardiomyopathic hamster heart cells
H. Kawaguchi, M. Shoki, H. Sano, T. Kudo, H. Sawa, H. Okamoto, Y. Sakata, H. Yasuda
Circulation Research, 69, 4, 1015, 1021, 1991, [Peer-reviewed]
English, Scientific journal

DISTRIBUTION OF ATRIAL-NATRIURETIC-PEPTIDE IN THE CONDUCTION SYSTEM AND VENTRICULAR MUSCLES OF THE HUMAN HEART
N MOCHIZUKI, H SAWA, H YASUDA, T SHINOHARA, K NAGASHIMA, T YAMAJI, N OHNUMA, WW HALL
VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY, 418, 1, 9, 16, 1991, [Peer-reviewed]
English, Scientific journal

ENDOTHELIN STIMULATES ANGIOTENSIN-I TO ANGIOTENSIN-II CONVERSION IN CULTURED PULMONARY-ARTERY ENDOTHELIAL-CELLS
H KAWAGUCHI, H SAWA, H YASUDA
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 22, 8, 839, 842, Aug. 1990
English

Mechanism of increased angiotensin-converting enzyme activity stimulated by platelet-activating factor
Hideaki Kawaguchi, Hirofumi Sawa, Hisakazu Yasuda
BBA - Molecular Cell Research, 1052, 3, 503, 508, 22 May 1990, [Peer-reviewed]
English, Scientific journal

MECHANISM OF INCREASED ANGIOTENSIN-CONVERTING ENZYME-ACTIVITY STIMULATED BY PLATELET-ACTIVATING FACTOR
H KAWAGUCHI, H SAWA, H YASUDA
BIOCHIMICA ET BIOPHYSICA ACTA, 1052, 3, 503, 508, May 1990
English, Scientific journal

Kawaguchi H, Sawa H, Iizuka K, Yasuda H: Platelet-activating factor stimulates angiotensin converting enzyme activity. J Hypertens 8: 173-177, 1990*　　　　　　　　　　　　　　　
1990

Kawaguchi H, Sawa H, Yasuda H: Effect of atrial natriuretic factor on angiotensin converting enzyme. J Hypertens 8: 749-753, 1990*　　　　　　　　　　　　　　　
1990

Platelet-activating factor stimulates angiotensin converting enzyme activity
Hideaki Kawaguchi, Hirofumi Sawa, Kenji Iizuka, Hisakazu Yasuda
Journal of Hypertension, 8, 2, 173, 177, 1990, [Peer-reviewed]
English, Scientific journal

Effect of atrial natriuretic factor on angiotensin converting enzyme
Hideaki Kawaguchi, Hirofumi Sawa, Hisakazu Yasuda
Journal of Hypertension, 8, 8, 749, 753, 1990, [Peer-reviewed]
English, Scientific journal

POSITIVE TRANSMISSION OF CREUTZFELDT-JAKOB DISEASE VERIFIED BY MURINE KURU PLAQUES
T KITAMOTO, J TATEISHI, H SAWA, K DOHURA
LABORATORY INVESTIGATION, 60, 4, 507, 512, Apr. 1989, [Peer-reviewed]
English, Scientific journal

Kawaguchi H, Sawa H, Yasuda H: Effect of atrial natriuretic factor on angiotensin converting enzyme. J Mol Cell Cardiol 21: 959-961, 1989*　　　　　　　　　　　　　　　
1989

Visualization of liver on bone scintigraphy during treatment with iron chondroitin sulfate colloid
S. Tanaka, H. Sawa, T. Fukuda
Kakuigaku, 20, 8, 1175, 1181, 1983, [Peer-reviewed]
Japanese, Scientific journal

Analysis of the effect of Ubiquitin-associated protein 2-like which binds to West Nile virus capsid protein on viral replication
小林進太郎, 前園佳祐, 高橋優奈, 神谷亘, 好井健太朗, 澤洋文, 澤洋文, 苅和宏明, 日本ウイルス学会学術集会プログラム・予稿集(Web), 71st, 2024

Structural analysis of SARS-CoV-2 using BSL3 cryo-EM
福原秀雄, DOKAINISH Hisham, 喜多俊介, 田畑耕史郎, 田畑耕史郎, 高巣晃, HUISKONEN Juha, 安楽佑樹, 千田俊哉, 千田俊哉, 千田俊哉, STUART David, 佐々木道仁, 大場靖子, 鈴木定彦, 鈴木定彦, 澤洋文, 澤洋文, 前仲勝実, 前仲勝実, 前仲勝実, 日本生体防御学会学術総会講演抄録集, 35th (Web), 2024

Structural basis for antiviral activity of a nucleoside analogue targeting dengue virus RNA-dependent RNA polymerase
伊東詩織, 喜多俊介, 上村健太朗, 上村健太朗, 上村健太朗, 上村健太朗, 岩間湧希, 田所高志, 澤洋文, 澤洋文, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 松田彰, 前仲勝実, 前仲勝実, 前仲勝実, 日本薬学会年会要旨集(Web), 144th, 2024

IgA抗体の自己重合反応による四量体形成とその応用
田畑耕史郎, 田畑耕史郎, 田畑耕史郎, 安楽佑樹, 多賀祐喜, 佐々木道仁, 佐々木道仁, 板倉友香里, 板倉友香里, 後藤希代子, 長谷川秀樹, 前仲勝実, 前仲勝実, 澤洋文, 澤洋文, 澤洋文, 福原秀雄, 大場靖子, 大場靖子, 鈴木忠樹, 日本抗体学会学術大会プログラム・抄録集(Web), 2nd, 2023

Generation of severe COVID-19 mouse model by treatment with Cyclophosphamide
日下部伸治, 日下部伸治, 鳥羽晋輔, 鳥羽晋輔, 井澤政明, 丸山優樹, 丸山優樹, 上村健太朗, 上村健太朗, 上村健太朗, 宍戸貴雄, 佐々木道仁, 大場靖子, 澤洋文, 澤洋文, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Genetic characterization of various herpesviruses in bats in Zambia
播磨勇人, 邱永晋, 山岸潤也, 梶原将大, CHANGULA Katendi, 佐々木道仁, MWEENE Aaron S, 澤洋文, 石原加奈子, HANG’OMBE Bernard M, 高田礼人, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Establishment of antiviral neutralizing antibody targeting intracellular process of viral replication
板倉友香里, 板倉友香里, 田畑耕史郎, 田畑耕史郎, 大場靖子, 大場靖子, 大場靖子, 澤洋文, 澤洋文, 澤洋文, 佐々木道仁, 佐々木道仁, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Mechanism of severe COVID-19 regulated by amino acid mutations in non-structural proteins
岸本麻衣, 岸本麻衣, 鳥羽晋輔, 鳥羽晋輔, 上村健太朗, 上村健太朗, 上村健太朗, 丸山優樹, 丸山優樹, 日下部伸治, 日下部伸治, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 大場靖子, 澤洋文, 澤洋文, 佐々木道仁, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Broad-spectrum search for influenza virus CEN (cap endonuclease) inhibitors
佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 鳥羽晋輔, 鳥羽晋輔, 垰田善之, 日下部伸治, 日下部伸治, 小西慧, 小西慧, 松野啓太, 松野啓太, 吉松組子, 有川二郎, 佐々木道仁, 佐々木道仁, 大場靖子, 大場靖子, 大場靖子, 澤洋文, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Pathogenicity analysis of two strains of West Nile virus newly isolated from mosquito and crocodile in Zambia
小林広子, 田畑耕史郎, 有泉拓馬, CHAMBARO Herman, PHONGPHAEW Wallaya, SIMULUNDU Edgar, 佐々木道仁, 澤洋文, 澤洋文, 澤洋文, 大場靖子, 大場靖子, 大場靖子, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Investigation of anti-Nairovirus compounds
鳥羽晋輔, 鳥羽晋輔, 平野港, 垰田善之, 日下部伸治, 日下部伸治, 小西慧, 小西慧, 丸山優樹, 宍戸貴雄, 好井健太朗, 佐々木道仁, 大場靖子, CHANGULA Katendi, MUDENDA Hang’ombe Bernard, 澤洋文, 澤洋文, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Comparison of the viral infectivity between the fixed and street strains of Rabies virus in peripheral tissues
川口虹穂, 板倉友香里, 井上智, 前田健, 伊藤直人, 澤洋文, 澤洋文, 大場靖子, 大場靖子, 佐々木道仁, 佐々木道仁, 日本分子生物学会年会プログラム・要旨集(Web), 46th, 2023

Discovery history of novel oral drug S-217622 (ensitrelvir) for COVID-19
加藤輝久, 登治謙, 川島生, 丸山優樹, 鳥羽晋輔, 鳥羽晋輔, 佐名木孝央, 宇納佑斗, 中原健二, 垰田善之, 上原彰太, 山本志保, 水垂亨, 笠松幸司, 幸木謙典, 中橋徳文, 須藤貴弘, 佐々木道仁, 大場靖子, 澤洋文, 澤洋文, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 佐藤剛章, 立花裕樹, 日本薬学会年会要旨集(Web), 143rd, 2023

Temperature-dependent regulatory mechanism of infectivity on Insect-Specific Flavivirus
小林広子, 田畑耕史郎, 佐々木道仁, 佐々木道仁, 澤洋文, 澤洋文, 澤洋文, 大場靖子, 大場靖子, 大場靖子, 日本分子生物学会年会プログラム・要旨集(Web), 46th, 2023

Discovery of a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses
上村健太朗, 上村健太朗, 上村健太朗, 上村健太朗, 上村健太朗, 登治謙, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 鳥羽晋輔, 鳥羽晋輔, 日下部伸治, 日下部伸治, 佐々木道仁, 田畑耕史郎, 大場靖子, 澤洋文, 澤洋文, 松浦善治, 松浦善治, 松田彰, 前仲勝実, 前仲勝実, 前仲勝実, 日本薬学会年会要旨集(Web), 143rd, 2023

血管内皮細胞におけるSARS-CoV-2侵入機構の解析
桜井優弥, 間石奈湖, 藤岡容一朗, 大場雄介, 武田遼, 佐々木道仁, 大場靖子, 樋田泰浩, 澤洋文, 澤洋文, 樋田京子, 日本血管生物医学会学術集会プログラム・抄録集, 31st (CD-ROM), 2023

X-206 exhibits broad-spectrum and robust inhibition against infections by several drug-resistant isolates and variants of SARS-CoV-2.
佐々木慈英, 岡部伊織, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 児玉耕太, 乙黒聡子, 佐々木道仁, 大場靖子, 澤洋文, 澤洋文, 前仲勝実, 柳雄介, 橋口隆生, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Combination therapy with oral antiviral and anti-inflammatory treatments improves the delayed-therapeutic effect on COVID-19
佐々木道仁, 杉達紀, 飯田俊, 平田雄一郎, 日下部伸治, 日下部伸治, 小西慧, 小西慧, 板倉友香里, 板倉友香里, 田畑耕史郎, 田畑耕史郎, 岸本麻衣, 岸本麻衣, 小林広子, 有泉拓馬, KITTIYA Intaruck, 登治謙, 鳥羽晋輔, 鳥羽晋輔, 佐藤彰彦, 佐藤彰彦, 佐藤彰彦, 松野啓太, 松野啓太, 山岸潤也, 山岸潤也, 鈴木忠樹, 大場靖子, 大場靖子, 澤洋文, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

ザンビアのエジプトルーセットオオコウモリおよびマストミスから分離されたロタウイルスAの性状解析
岸本麻衣, 岸本麻衣, 梶原将大, 高田礼人, 大園誠也, 鈴木忠樹, 伊藤直人, 大場靖子, 澤洋文, 澤洋文, 佐々木道仁, 日本獣医学会学術集会講演要旨集, 166th, 2023

Genes involved in spread of SARS-CoV-2 into the lower respiratory tract may be under adaptive selection.
高田光輔, 大場靖子, 木田裕里恵, 呉佳齊, 小野慎子, 小野慎子, 松浦善治, 松浦善治, 中川草, 澤洋文, 渡辺登喜子, 渡辺登喜子, 日本進化学会大会プログラム・講演要旨集(Web), 25th, 2023

5-Ethynylimidazole-4-carboxamide(EICA)ヌクレオチドプロドラッグの合成と抗デングウイルス活性　　　　　　　　　　　　　　　
日野谷 直人, 中村 元紀, 田良島 典子, 大場 靖子, 澤 洋文, 松田 彰, 前仲 勝実, 南川 典昭, 日本薬学会年会要旨集, 142年会, 28S, pm03S, Mar. 2022
(公社)日本薬学会, Japanese

SARS-CoV-2スパイクタンパク質の切断と細胞融合活性・病原性の関連
瓜生慧也, HESHAM Nasser, 鈴木理滋, 岸本麻衣, 澤洋文, 福原崇介, 池田輝政, 佐藤佳, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th, 2022

ザンビアにおけるクリミア・コンゴ出血熱の疫学調査
梶原将大, SIMUUNZA Martin, SAASA Ngonda, DAUTU George, 森亜紀奈, 邱永晋, 中尾亮, HANG’OMBE Bernard, HANG’OMBE Bernard, 澤洋文, 澤洋文, SIMULUNDU Edgar, 福士秀悦, 森川茂, 西條政幸, 有川二郎, 高田礼人, 高田礼人, 吉松組子, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th, 2022

SARS-CoV-2感染マウスを用いた肺血管内皮細胞の重症化関連遺伝子の解析
武田遼, 武田遼, 伊藤航, 手代木孝仁, 佐々木道仁, 大場靖子, 大場靖子, 間石奈湖, 松田彩, 佐藤彰彦, 鳥羽晋輔, 李智媛, 飯村忠浩, 樋田泰浩, 北川善政, 澤洋文, 澤洋文, 澤洋文, 樋田京子, 日本血管生物医学会学術集会プログラム・抄録集, 30th (CD-ROM), 2022

人と動物の健康を守るワンヘルスの取組み-北海道大学One Healthリサーチセンターの活動紹介-
堀内基広, 池中良徳, 山崎淳平, 佐藤豊孝, 鈴木章夫, 直亨則, 松野啓太, 澤洋文, 日本獣医師会獣医学術学会年次大会講演要旨集, 2022, 2022

SARS-CoV-2BA.2株に由来する亜株の性状解析
木村出海, 山岨大智, 山岨大智, 田村友和, 直亨則, 直亨則, 伊東潤平, 松野啓太, 松野啓太, 松野啓太, 澤洋文, 澤洋文, 澤洋文, 福原崇介, 佐藤佳, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th, 2022

狂犬病ウイルスL蛋白質に存在するNPYNE配列はウイルス複製に重要である
泉郁輝, 牧野真知子, 佐々木道仁, 中川賢人, 高橋龍樹, 岡田和真, 藤井祐至, 西山祥子, 正谷達謄, 正谷達謄, 澤洋文, 杉山誠, 伊藤直人, 伊藤直人, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th, 2022

マウス感染モデルを用いたCOVID-19重症化における血管病態の解析
積田卓也, 武田遼, 澤洋文, 佐々木道仁, 間石奈湖, 樋田泰浩, 松田彩, 佐藤彰彦, 佐藤彰彦, 鳥羽晋輔, 鳥羽晋輔, 田中宏典, 樋田京子, 高血圧関連疾患モデル学会学術総会抄録集, 57th (CD-ROM), 2021

Characterization of a Nelson Bay orthoreovirus isolated from an Egyptian fruit bat in Zambia
播磨勇人, 佐々木道仁, 大場靖子, 邱永晋, チャングラカテンディ, 梶原将大, シムルンドゥエドガー, 谷口怜, 高田礼人, 西條政幸, ハンゴンべバーナード, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 68th, 2021

Glycoprotein Analyses by Mass Spectrometry
梶裕之, 富岡あづさ, 日尾野隆大, 日尾野隆大, 佐々木道仁, 大場靖子, 澤洋文, 久野敦, 質量分析総合討論会講演要旨集, 69th, 2021

RIG-Iはヒト肺細胞においてシグナル伝達非依存的な抗SARS-CoV-2防御を誘導する
山田大翔, 山田大翔, 佐藤精一, 佐藤精一, 外山雄貴, 外山雄貴, 大場靖子, 澤洋文, 山内肇, 佐々木道仁, 高岡晃教, 高岡晃教, 日本インターフェロン・サイトカイン学会学術集会抄録集, 85th (CD-ROM), 2021

G蛋白質333位のアミノ酸残基が規定する狂犬病ウイルスの病原性発現機構の解析
板倉友香里, 田畑耕史郎, 伊藤直人, 大場靖子, 澤洋文, 佐々木道仁, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

ボリビア多民族国サンタクルス県の牛におけるBabesiaおよびAnaplasmaの感染状況
小方昌平, PEREIRA Juan Antonio, 松野啓太, 大場靖子, 澤洋文, 川森文彦, 野中成晃, 中尾亮, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

北海道産ヤマトヤブカにおけるジカウイルス感受性の評価
川江詩乃, 岩本夏奈, 江下優樹, 大場靖子, 澤洋文, 村松康和, 内田玲麻, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

ヤマトヤブカ体内におけるジカウイルスのQuasispecies評価
三木要, 岩本夏奈, 江下優樹, 大場靖子, 澤洋文, 村松康和, 内田玲麻, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

ザンビアに生息する野生げっ歯類動物における脳心筋炎ウイルス(EMCV)の疫学調査
岸本麻衣, HANG’OMBE Bernard M., 大場靖子, 澤洋文, 佐々木道仁, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

ザンビアのブタにおける消化管ウイルスの疫学調査
播磨勇人, 梶原将大, 佐々木道仁, SIMULUNDU Edgar, BWALYA Eugene, 邱永晋, 奥谷公亮, 大場靖子, HANG’OMBE Bernard M, MWEENE Aaron S, 高田礼人, 澤洋文, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

質量分析とレクチンアレイを組み合わせたSARS-CoV-2スパイクタンパク質の高精度糖鎖構造解析
日尾野隆大, 日尾野隆大, 富岡あづさ, 梶裕之, 佐々木道仁, 大場靖子, 澤洋文, 久野敦, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

Characterization of a newly emerging orthonairovirus in Hokkaido, Japan
有泉拓馬, 山口宏樹, 澤洋文, 大場靖子, 松野啓太, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

Evaluation of cell-penetrating peptides for the production of intracellular invasive antiviral neutralizing antibody
板倉友香里, 田畑耕史郎, 大場靖子, 澤洋文, 澤洋文, 佐々木道仁, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

A mechanism of Ig variable region-independent oligomerization of secretory IgA antibody accelerated by polymeric Ig receptor.
田畑耕史郎, 田畑耕史郎, 鈴木忠樹, 佐野芳, 齊藤慎二, 相内章, 佐々木道仁, 長谷川秀樹, 大場靖子, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

SARS-CoV-2 variants are generated during propagation in Vero cells
佐々木道仁, 上村健太朗, 上村健太朗, 鳥羽晋輔, 鳥羽晋輔, 佐藤彰彦, 佐藤彰彦, 板倉友香里, INTARUCK Kittiya, 岸本麻衣, 田畑耕史郎, CHAMBARO Herman, 大場靖子, 大場靖子, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

Examination of the accumulation of TDP-43 observed in neuronal cells infected with West Nile virus
小林進太郎, 好井健太朗, 松野啓太, 大場靖子, 澤洋文, 苅和宏明, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

Investigation of an orthoreovirus isolated from a fruit bat in Zambia
播磨勇人, 佐々木道仁, 大場靖子, QIU Yongjin, 梶原将大, 谷口怜, 高田礼人, 西條政幸, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

Identification of host type II transmembrane serine proteases which promote SARS-CoV-2 infection
岸本麻衣, 上村健太朗, 上村健太朗, 佐名木孝央, 佐名木孝央, 佐藤彰彦, 佐藤彰彦, 大場靖子, 澤洋文, 佐々木道仁, 日本分子生物学会年会プログラム・要旨集(Web), 44th, 2021

Arthropod-borne viruses (arboviruses)
大場靖子, 澤洋文, 松野啓太, 松野啓太, ウイルス, 70, 1, 3, 14, 2020, [Domestic magazines]
"Arbovirus" is a term for a virus transmitted to mammals by hematophagous arthropods; arboviruses; replicate in both mammals and arthropods. Since the life cycle of arboviruses is highly dependent on arthropods, control of the arthropods (vectors) is generally considered important for the control of arbovirus infection. Various pathogens that cause diseases in the medical and veterinary fields are grouped into arboviruses with a history of their discoveries since the early 20th century. Furthermore, because of recent advances in sequencing technology, new arboviruses have been discovered one after another. Here we would like to overview the known arboviruses and their infections., Japanese

エンベロープタンパク質のアミノ酸変異によるウエストナイルウイルスの増殖および病態形成への影響　　　　　　　　　　　　　　　
小林 進太郎, 金子 知里, 川上 怜子, 長谷部 理絵, 澤 洋文, 好井 健太朗, 苅和 宏明, 日本獣医学会学術集会講演要旨集, 162回, 431, 431, Aug. 2019
(公社)日本獣医学会, Japanese

豚コレラウイルスワクチン株感染による細胞死誘導と細胞変性効果
板倉友香里, 板倉友香里, 松野啓太, 松野啓太, 伊藤麻子, 藤本悠理, 田村友和, 亀山健一郎, 岡松正敏, NICOLAS Ruggli, NICOLAS Ruggli, 喜田宏, 喜田宏, 澤洋文, 澤洋文, 迫田義博, 迫田義博, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

エンベロープタンパク質の159番目のアミノ酸のウエストナイルウイルスの増殖および病原性発現に与える影響
小林進太郎, 金子知里, 川上怜子, 長谷部理絵, 澤洋文, 好井健太朗, 苅和宏明, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

Autopsy findings in the early stage of amyotrophic lateral sclerosis with “dropped head” syndrome
Tanikawa Satoshi, Tanino Mishie, Wang Lei, Ishikawa Marin, Miyazaki Masaya, Tsuda Masumi, Tsuda Masumi, Tsuda Masumi, Orba Yasuko, Sawa Hirofumi, Matoba Kotarou, Nakamura Nishio, Nagashima Kazuo, Hall William W., Tanaka Shinya, Tanaka Shinya, Tanaka Shinya, Neuropathology (Web), 39, 5, 374, 377, 2019, [International Magazine]
Dropped head syndrome (DHS) has been rarely observed in amyotrophic lateral sclerosis (ALS), and the neuropathological findings of this condition have almost never been described. The identification of transactivation response DNA-binding protein 43 kDa (TDP-43), which binds to RNA/DNA has provided a new method for studying ALS and frontotemporal lobar degeneration (FTLD). Post-mortem examination of an adult sudden death case of a 71-year-old patient who complained of DHS exhibited severe loss of anterior motor neurons in the cervical cord (C4-6). Loss of nerve fibers of the anterior roots was striking compared with posterior roots, together with marked neurogenic atrophy of posterior muscles semispinalis cervicis. Bunina bodies were found in large neurons of Betz giant cells, but not in the motor neurons of spinal cords, or neurons of bulbar regions. Phosphorylated TDP-43 (p-TDP-43)-positive structures were detected in the residual neurons of the cervical, thoracic and lumber cords, hypoglossal nucleus, cerebellar dentate nucleus and parahippocampal cortex, together with ubiquitin-positive inclusions. Phosphorylated Tau positive structures in neuronal cytoplasm were found in the amygdala, entorhinal cortex and parahippocampal cortex, some of which co-expressed p-TDP-43. The medial zone of cervical cords may be the first onset site, and that is the cause of head drop in the early stage of ALS. In spite of detailed examination, the direct cause of sudden death was not verified. This autopsy report revealed the relation of DHS which is a rare clinical manifestation of ALS, and neuropathological findings., English

In vitroにおける四量体分泌型IgA抗体形成機構の解明
田畑耕史郎, 田畑耕史郎, 鈴木忠樹, 佐野芳, 齊藤慎二, 相内章, 大場靖子, 長谷川秀樹, 長谷川秀樹, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019

インターフェロン受容体欠損マウスにおける狂犬病ウイルス病原性発現機構
板倉友香里, 大場靖子, 澤洋文, 澤洋文, 佐々木道仁, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019

ウエストナイルウイルス感染で起こるAMP-activated protein kinaseの分解およびオートファジーの抑制による神経病態形成への影響
小林進太郎, 好井健太朗, PHONGPAEW Wallaya, 武藤芽未, 平野港, 大場靖子, 澤洋文, 苅和宏明, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019

ロタウイルス感染を促進させる宿主プロテアーゼの同定
佐々木道仁, 伊藤直人, 杉山誠, 大場靖子, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019

ESCRTタンパク質HGSはチクングニアウイルスのコードするタンパク質と相互作用し,細胞内増殖の2過程を制御する
鳥居志保, 鳥居志保, 大場靖子, 佐々木道仁, 和田雄治, HOBSON-PETERS Jody, HALL Roy A., 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019

蚊のゲノムに内在する多様なフラビウイルスエレメント
大場靖子, HANG’OMBE Bernard M., MWEENE Aaron S., 佐々木道仁, 江下優樹, 澤洋文, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019

ESCRT蛋白質HGSはチクングニアウイルスと相互作用し,細胞内増殖2過程を制御する
鳥居志保, 鳥居志保, 大場靖子, 佐々木道仁, 和田雄治, HOBSON-PETERS Jody, HALL Roy, 澤洋文, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

宿主タンパク質YB-1は狂犬病ウイルスmRNAに結合し遺伝子発現を促進する
佐々木道仁, 伊藤直人, 杉山誠, GONZALEZ Gabriel, 伊藤公人, 伊藤公人, 大場靖子, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

抗デングウイルス活性をもつ低分子化合物の探索
佐藤彰彦, 佐藤彰彦, 登治謙, 鳥羽晋輔, 鳥羽晋輔, 上村健太朗, 上村健太朗, 吉田立, 宍戸貴雄, 大場靖子, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

多種の蚊に内在するフラビウイルスエレメント
大場靖子, HANG’OMBE Bernard M., MWEENE Aaron S., 佐々木道仁, 江下優樹, 澤洋文, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

ザンビアのエジプトルーセットオオコウモリから検出されたマールブルグウイルスの遺伝学的解析
梶原将大, CHANGULA Katendi, HANG’OMBE Bernard, 播磨勇人, 宮本洋子, 衛藤芳樹, 奥谷公亮, 磯野真央, 吉田玲子, 邱永晋, 森(梶原)亜紀奈, 大場靖子, 澤洋文, 澤洋文, 小川寛仁, SIMULUNDU Edgar, SQUARRE David, MUKONKA Victor, MWEENE Aaron, 高田礼人, 高田礼人, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

ザンビアのダニで発見した新規フラビウイルスはフラビウイルス属の中で独特な系統を形成するNgoye virusに遺伝的に密接に関係している
播磨勇人, 鳥居志保, 邱永晋, 梶原将大, 衛藤芳樹, 大場靖子, 江下優樹, ハンゴンベ バーナード, 好井健太朗, シムンザ マーティン, 高田礼人, 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

狂犬病ウイルスに対して強い抗ウイルス活性を示す低分子化合物の同定
上村健太朗, 上村健太朗, 鳥羽晋輔, 鳥羽晋輔, 登治謙, 吉田立, 宍戸貴雄, 佐々木道仁, 伊藤直人, 大場靖子, 澤洋文, 澤洋文, 佐藤彰彦, 佐藤彰彦, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

LCMV感染マウスモデルを用いたCompound Xのin vivo PK/PD解析
鳥羽晋輔, 鳥羽晋輔, 登治謙, 上村健太朗, 上村健太朗, 垰田善之, 佐藤健司, 吉田立, 宍戸貴雄, 大場靖子, 澤洋文, 澤洋文, 佐藤彰彦, 佐藤彰彦, 日本ウイルス学会学術集会プログラム・予稿集(Web), 67th, 2019

マダニ中の多様なフレボウイルスは何者か?
松野啓太, 松野啓太, 中尾亮, 草木迫浩大, 大場靖子, 澤洋文, 澤洋文, 日本獣医学会学術集会講演要旨集, 162nd, 2019

ウエストナイルウイルス感染で起こるオートファジーの抑制と神経病態形成の関係　　　　　　　　　　　　　　　
小林 進太郎, 好井 健太朗, Wallaya Phongpaew, 武藤 芽未, 平野 港, 大場 靖子, 澤 洋文, 苅和 宏明, 日本獣医学会学術集会講演要旨集, 161回, 395, 395, Aug. 2018
(公社)日本獣医学会, Japanese

日本産ヒトスジシマカのジカウイルス媒介能
江下優樹, 江下優樹, 江下優樹, 江下優樹, 和田雄治, 林田京子, 山岸潤也, 杉本千尋, 佐々木道仁, 大場靖子, 澤洋文, 飛弾野真也, 神山長慶, 小林隆志, 高崎智彦, 加藤文博, 田島茂, 倉根一郎, LIM Chang Kweng, 衛生動物, 69, Supplement, 51, 30 Mar. 2018
Japanese

ウエストナイルウイルスのカプシドタンパク質によるオートファジーの抑制による変性タンパク質の蓄積と神経病態形成についての解析　　　　　　　　　　　　　　　
小林 進太郎, 好井 健太朗, Phonqphaew Wallaya, 武藤 芽未, 平野 港, 大場 靖子, 澤 洋文, 苅和 宏明, 生命科学系学会合同年次大会, 2017年度, [3P, 1110], Dec. 2017
生命科学系学会合同年次大会運営事務局, Japanese

ウイルス研究の最前線 2.ザンビア,インドネシアにおける野生動物が保有するDNAウイルスの探索
澤洋文, 澤洋文, 佐々木道仁, 大場靖子, ウイルス, 67, 2, 151‐160, 160, Dec. 2017
日本ウイルス学会, Japanese

本邦における進行性多巣性白質脳症(PML)サーベイランスの現状 PMLサーベイランス委員会報告　　　　　　　　　　　　　　　
三浦 義治, 中道 一生, 西條 政幸, 高橋 健太, 鈴木 忠樹, 阿江 竜介, 濱口 毅, 原 由紀子, 三條 伸夫, 雪竹 基弘, 岸田 修二, 澤 洋文, 奴久妻 総一, 水澤 英洋, 山田 正仁, NEUROINFECTION, 22, 2, 246, 246, Sep. 2017
日本神経感染症学会, Japanese

狂犬病ウイルスの細胞吸着に関与する宿主因子の解析
佐々木道仁, アニンディタ パウリナ, 伊藤直人, 杉山誠, 福原秀雄, 尾瀬農之, 尾瀬農之, 前仲勝実, 澤洋文, 澤洋文, 日本獣医学会学術集会講演要旨集, 160th, 400, 400, 30 Aug. 2017
(公社)日本獣医学会, Japanese

狂犬病ウイルスの細胞吸着に関与する宿主因子の解析　　　　　　　　　　　　　　　
佐々木 道仁, アニンディ・タパウリナ, 伊藤 直人, 杉山 誠, 福原 秀雄, 尾瀬 農之, 前仲 勝実, 澤 洋文, 日本獣医学会学術集会講演要旨集, 160回, 400, 400, Aug. 2017
(公社)日本獣医学会, Japanese

In vitroでの狂犬病ウイルスに対する5-エチニル-1-リボフラノシルイミダゾール-4-カルボキサミド(EICAR)の抗ウイルス活性に関する検討(Examination of antiviral activity of 5-ethynyl-1-ribofuranosylimidazole-4-carboxamide(EICAR) against rabies virus in vitro)　　　　　　　　　　　　　　　
Anindita Paulina Duhita, 佐々木 道仁, 伊藤 直人, 杉山 誠, 南川 典昭, 周東 智, 乙黒 聡子, 市川 聡, 松田 彰, 前仲 勝実, 大場 靖子, 澤 洋文, 日本獣医学会学術集会講演要旨集, 160回, 390, 390, Aug. 2017
(公社)日本獣医学会, English

Examination of antiviral activity of 5-ethynyl-1-ribofuranosylimidazole-4-carboxamide(EICAR) against rabies virus in vitro(和訳中)　　　　　　　　　　　　　　　
Anindita Paulina Duhita, 佐々木 道仁, 伊藤 直人, 杉山 誠, 南川 典昭, 周東 智, 乙黒 聡子, 市川 聡, 松田 彰, 前仲 勝実, 大場 靖子, 澤 洋文, 日本獣医学会学術集会講演要旨集, 160回, 390, 390, Aug. 2017
(公社)日本獣医学会, English

【One Healthの視点からみた感染症の現状と対策】 野生動物が保有するウイルスを対象とする研究
佐々木 道仁, 大場 靖子, 澤 洋文, 最新医学, 72, 4, 508, 512, Apr. 2017
(株)最新医学社, Japanese

本邦発症の進行性多巣性白質脳症患者に対する塩酸メフロキン治療の有効性に関する検討　　　　　　　　　　　　　　　
三浦 義治, 池内 和彦, 岸田 修二, 中道 一生, 西條 政幸, 高橋 健太, 鈴木 忠樹, 三條 伸夫, 阿江 竜介, 中村 好一, 澤 洋文, 長嶋 和郎, 奴久妻 総一, 原 由紀子, 雪竹 基弘, 浜口 毅, 水澤 英洋, 山田 正仁, 臨床神経学, 56, Suppl., S292, S292, Dec. 2016
(一社)日本神経学会, Japanese

進行性多巣性白質脳症の診断・治療の新展開 PMLの診断と治療　　　　　　　　　　　　　　　
三浦 義治, 岸田 修二, 中道 一生, 西條 政幸, 高橋 健太, 鈴木 忠樹, 三條 伸夫, 阿江 竜介, 澤 洋文, 奴久妻 聡一, 宍戸 由紀子[原], 雪竹 基弘, 浜口 毅, 水澤 英洋, 山田 正仁, NEUROINFECTION, 21, 2, 172, 172, Sep. 2016
日本神経感染症学会, Japanese

PMLとPMLサーベイランス　　　　　　　　　　　　　　　
三條 伸夫, 宍戸 由紀子[原], 中道 一生, 西條 政幸, 三浦 義治, 雪竹 基弘, 高橋 健太, 鈴木 忠樹, 岸田 修二, 澤 洋文, 中村 好一, 浜口 毅, 山田 正仁, 水澤 英洋, 横田 隆徳, NEUROINFECTION, 21, 2, 192, 192, Sep. 2016
日本神経感染症学会, Japanese

本邦発症進行性多巣性白質脳症患者に対する塩酸メフロキン治療の多数例における有効性の解析　　　　　　　　　　　　　　　
三浦 義治, 中道 一生, 西條 政幸, 岸田 修二, 高橋 健太, 鈴木 忠樹, 三條 伸夫, 阿江 竜介, 澤 洋文, 奴久妻 聡一, 原 由紀子, 雪竹 基弘, 浜口 毅, 水澤 英洋, 山田 正仁, NEUROINFECTION, 21, 2, 229, 229, Sep. 2016
日本神経感染症学会, Japanese

ザンビア共和国に飛来するストローオオコウモリ(Eidolon helvum)から分離されたアデノウイルスの性状解析と分子疫学的解析
小川寛人, 小川寛人, 小川寛人, 梶原将大, 直亨則, 丸山隼輝, 上野恵介, 石井秋宏, 石井秋宏, 藤倉大輔, HANG’OMBE Bernard, AARON Mweene, 山田雅夫, 東秀明, 東秀明, 澤洋文, 澤洋文, 高田礼人, 高田礼人, 日本獣医学会学術集会講演要旨集, 159th, 376, 376, 30 Aug. 2016
(公社)日本獣医学会, Japanese

ウエストナイルウイルスの粒子放出過程におけるRab8bタンパク質の役割　　　　　　　　　　　　　　　
小林 進太郎, 鈴木 忠樹, 川口 晶, Phongphaew Wallaya, 好井 健太朗, 苅和 宏明, 大場 靖子, 澤 洋文, 日本獣医学会学術集会講演要旨集, 159回, 409, 409, Aug. 2016
(公社)日本獣医学会, Japanese

ヘパラン硫酸を介した狂犬病ウイルスの細胞吸着機構の解析
佐々木道仁, アニンディタ パウリナ, 伊藤直人, 杉山誠, 福原秀雄, 尾瀬農之, 前仲勝実, 大場靖子, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.2P‐0314 (WEB ONLY), 2016
Japanese

ウエストナイルウイルス感染による変性タンパク質蓄積機構の解析　　　　　　　　　　　　　　　
小林 進太郎, Phongphaew Wallaya, 好井 健太朗, 平野 港, 武藤 芽未, 大場 靖子, 澤 洋文, 苅和 宏明, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1P1135], [1P1135], Dec. 2015
(公社)日本生化学会, English

本邦発症の進行性多巣性白質脳症患者サーベイランスの現状と課題 厚労科研PML研究班PMLサーベイランス報告　　　　　　　　　　　　　　　
三浦 義治, 中道 一生, 岸田 修二, 西條 政幸, 高橋 健太, 鈴木 忠樹, 三條 伸夫, 阿江 竜介, 澤 洋文, 奴久妻 総一, 原 由紀子, 雪竹 基弘, 濱口 毅, 水澤 英洋, 山田 正仁, NEUROINFECTION, 20, 2, 175, 175, Sep. 2015
日本神経感染症学会, Japanese

様々な血清型のListeria monocytogenesのマウス尾静脈接種モデルにおける病原性解析
長谷部理絵, 中尾亮, 平井佑治, 鈴木章夫, 山崎剛士, 澤洋文, 高井伸二, 堀内基広, 日本獣医学会学術集会講演要旨集, 158th, 375, 30 Aug. 2015
Japanese

Potential viral pathogens in wild rodents and bats in Africa
石井 秋宏, 澤 洋文, 医学のあゆみ, 253, 1, 37, 42, 04 Apr. 2015
医歯薬出版, Japanese

プリオン病及び遅発性ウイルス感染症の分子病態解明・治療法開発に関する研究 進行性多巣性白質脳症(PML)におけるJCウイルスタンパク質の発現様式の免疫組織学的検討
澤洋文, 鈴木忠樹, 大場靖子, プリオン病及び遅発性ウイルス感染症の分子病態解明・治療法開発に関する研究 平成26年度 委託業務成果報告書, 67, 70, 2015
Japanese

北海道産マダニからの新規フレボウイルスの検出
NAKAO RYO, KAJIWARA MASAHIRO, KYU EISHIN, MORI AKINA, NAO NAGANORI, MURAMATSU MIEKO, YOSHII KENTARO, KARIWA HIROAKI, SAWA HIROFUMI, SUGIMOTO CHIHIRO, TAKADA AYATO, 日本獣医学会学術集会講演要旨集, 157th, 451, 11 Aug. 2014
Japanese

次世代シーケンサーによるリステリア菌国内分離株のゲノム比較解析
HASEBE RIE, NAKAO RYO, HIRAI YUJI, SUZUKI AKIO, YAMASAKI TAKESHI, SAWA HIROFUMI, TAKAI SHINJI, HORIUCHI MOTOHIRO, 日本獣医学会学術集会講演要旨集, 157th, 445, 11 Aug. 2014
Japanese

Reinhard Kurth Honorary Lecture HTLV-I and Adult T Cell Leukemia/Lymphoma (ATLL) : Cellular and Molecular Basis of Transformation
William W. Hall, Hirofumi Sawa, Hideki Hasegawa, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 65, 54, 54, Apr. 2014
English, Summary international conference

RNase内包ウイルスカプセルの作製と内部でのRNA分解反応
杉村尚俊, 新倉謙一, 萩原恭二, 三友秀之, 伊藤嘉浩, 澤洋文, 長田義仁, 居城邦治, 高分子学会予稿集(CD-ROM), 63, 1, 2014

ウイルスカプセルの内部空間での配列特異的RNA分解反応
杉村尚俊, 新倉謙一, 萩原恭二, 三友秀之, 澤洋文, 居城邦治, 高分子学会予稿集(CD-ROM), 63, 2, 2014

Involvement of EphA2-mediated tyrosine phosphorylation of Shp2 in Shp2-regulated activation of extracellular signal-regulated kinase
K. Miura, Y. Wakayama, M. Tanino, Y. Orba, H. Sawa, M. Hatakeyama, S. Tanaka, H. Sabe, N. Mochizuki, Oncogene, 32, 5292, 5301, 07 Nov. 2013

Investigation of the role of JC virus VP1 cysteine residues
Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 19, 3, 301, 301, Jun. 2013
English, Summary international conference

進行性多巣性白質脳症(PML)の病態解明への分子アプローチ
鈴木忠樹, 澤洋文, 大場靖子, 片野晴隆, 佐藤由子, 長谷川秀樹, 長嶋和郎, 日本病理学会会誌, 102, 1, 207, 26 Apr. 2013
Japanese

オートファジーはウエストナイルウイルスの増殖を抑制する
小林進太郎, 大場靖子, 山口宏樹, 佐々木道仁, 長谷部理絵, 木村享史, 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 61st, 2013

酵素内包ウイルスカプセルの作製と微小空間での酵素反応
杉村尚俊, 新倉謙一, 萩原恭二, 三友秀之, 永井健治, 澤洋文, 居城邦治, 高分子学会予稿集(CD-ROM), 62, 2, 2013

霊長類動物からの新規ポリオーマウイルスの検出
山口宏樹, 小林進太郎, 石井秋宏, 小川寛人, 木村享史, 澤洋文, 大場靖子, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2013

インフルエンザウイルス感染におけるマウス肺の病理学的変化の観察
澤洋文, MUTO Mton‐Akio, 寸田祐嗣, 服部ともえ, 藤倉大輔, 中山洋佑, 宮崎忠昭, 丸山光生, 木村享史, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 334, 31 Oct. 2012
Japanese

ザンビアの野生動物におけるオルソポックスウイルス感染の疫学調査
大場靖子, 石井秋宏, トーマス 由佳, 小川寛人, 中村一郎, 木村享史, 森川茂, 西條政幸, 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 443, 31 Oct. 2012
Japanese

JC virus encephalopathy is associated with a novel Agnoprotein-deletion JCV variant
Xin Dang, Christian Wuethrich, Jennifer Gordon, Hirofumi Sawa, Igor Koralnik, JOURNAL OF NEUROVIROLOGY, 18, 27, 27, May 2012
English, Summary international conference

Glutathione-triggered drug release from virus capsules in cells
Kenichi Niikura, Keita Nagakawa, Yusuke Musashi, Hirofumi Sawa, Masataka Kinjo, Kuniharu Ijiro, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 243, Mar. 2012
English, Summary international conference

Shape dependent immunogenicity of antigen-coated gold nanomaterials
Tatsuya Matsunaga, Kenichi Niikura, Tadaki Suzuki, Shintaro Kobayashi, Hiroki Yamaguchi, Hirofumi Sawa, Kuniharu Ijiro, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 243, Mar. 2012
English, Summary international conference

ウエストナイルウイルス感染神経細胞におけるユビキチン化タンパク質の蓄積
小林進太郎, 小林進太郎, 大場靖子, 山口宏樹, 木村享史, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012

形状の異なる金ナノ粒子を用いた擬似ウイルス粒子の作成とワクチン活性の形状依存性
松永達也, 新倉謙一, 鈴木忠樹, 小林進太郎, 山口宏樹, 澤洋文, 居城邦治, 日本DDS学会学術集会プログラム予稿集, 28th, 2012

霊長類動物におけるパラインフルエンザウイルスの疫学調査
佐々木道仁, 石井秋宏, 大場靖子, トーマス由佳, 小川寛人, 中村一郎, 木村享史, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012

ザンビアにおける霊長類動物からの新規ポリオーマウイルスの検出
山口宏樹, 山口宏樹, 大場靖子, 小林進太郎, 小林進太郎, 石井秋宏, 小川寛人, 中村一郎, THOMAS由佳, 木村享史, 澤洋文, 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012

霊長類動物におけるパラインフルエンザウイルス3型の疫学調査
佐々木道仁, 石井秋宏, 大場靖子, THOMAS Yuka, 小川寛人, 中村一郎, 木村享史, 澤洋文, 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 35th, 2012

ダチョウ肝臓に発現する異物代謝酵素の配列解析
川合佑典, 渡邉研右, 石井秋宏, 大沼愛子, 澤洋文, 池中良徳, 石塚真由美, 日本進化学会大会プログラム・講演要旨集(Web), 14th, 2012

Identification of the plague reservoir in an endemic area of Zambia
Bernard M. Hang'Ombe, I. Nakamura, D. Kaile, A. S. Mweene, K. L. Samui, B. S. Kilonzo, H. Sawa, C. Sugimoto, B. Wren, Onderstepoort Journal of Veterinary Research, 79, 2, 2012
AOSIS (pty) Ltd, English, Report scientific journal

ウマMHC class Iが示すウマヘルペスウイルス1型レセプター機能の解析
佐々木道仁, 五十嵐学, 澤洋文, 伊藤公人, 福士秀人, 木村享史, 日本獣医学会学術集会講演要旨集, 152nd, 239, 239, 31 Aug. 2011
(公社)日本獣医学会, Japanese

糖鎖認識を利用した金属ナノ粒子の集合化によるウイルス検出
永川桂大, 新倉謙一, 野村尚生, 松尾保孝, 鈴木忠樹, 澤洋文, 居城邦治, バイオ・高分子シンポジウム講演要旨集, 21st, 29-30, 15 Jul. 2011
Japanese

ウイルス粒子の再集合における金属ナノ粒子内包条件の検討
永川桂大, 新倉謙一, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, ナノ学会大会講演予稿集, 9th, 113, 02 Jun. 2011
Japanese

ウイルス様ナノカプセルを包含した金ナノシェル型構造体の構築
永川桂大, 野村尚生, 新倉謙一, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 日本化学会講演予稿集, 91st, 3, 989, 11 Mar. 2011
Japanese

ザンビア共和国の霊長類動物におけるポリオーマウイルスの疫学調査
山口宏樹, 小林進太郎, 大場靖子, 石井秋宏, 小川寛人, Thomas由佳, 木村享史, 澤洋文, 日本獣医学会学術集会講演要旨集, 152nd, 2011

特別講演 進行性多巣性白質脳症(PML)の原因ウイルスであるJCウイルスの細胞内動態 (第3回信州NeuroCPC)
澤 洋文, 高 昌星, 信州医学雑誌, 59, 3, 202, 207, 2011
信州医学会, Japanese

Progressive multifocal leukoencephalopathy (PML)
Hidehiro Mizusawa, Shuji Kishida, Masayuki Saijo, Motohiro Yukishita, Yukiko Shishido-Hara, Hirohumi Sawa, Kazuo Nagashima, Souichi Nukuzuma, Masahito Yamada, Clinical Neurology, 51, 11, 1051, 1057, 2011
Japanese

分子シャペロンCdc37/Hsp90はTaxの細胞内安定性とNF‐κB誘導活性を規定する
池辺詠美, 川口晶, 中野聡子, 八尋隆明, 田村陽介, 松本昂, 三井孝広, 仙波和代, 緒方正男, 堀光雄, 澤洋文, 田中勇悦, 西園晃, 長谷川秀樹, 伊波英克, 生化学, 83回・33回, 3P, 0993, Dec. 2010
(公社)日本生化学会, Japanese

野生齧歯動物からの新規ポリオーマウイルスの検出
大場靖子, 小林進太郎, 中村一郎, 石井秋宏, 木村享史, 澤洋文, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 445, 15 Oct. 2010
Japanese

A novel deletion in JC Virus agnoprotein causes productive infection of cortical pyramidal neurons
Xin Dang, Christian Wuthrich, Jennifer Gordon, Hirofumi Sawa, Igor Koralnik, JOURNAL OF NEUROVIROLOGY, 16, 24, 24, Oct. 2010
English, Summary international conference

Disruption of Intracellular Vesicular Trafficking by Agnoprotein is Essential for Viroporin Activity and JC Virus Replication
Tadaki Suzuki, Yasuko Orba, Yoshinori Malcino, Yuki Okada, Yuji Sunden, Takashi Kimura, Hideki Hasegawa, Tetsutaro Sata, William W. Hall, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 16, 84, 84, Oct. 2010
English, Summary international conference

Large T antigen promotes JC virus replication in G2 arrest by inducing G2 checkpoint signaling
Yasuko Orba, Tadaki Suzuki, Takashi Kimura, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 16, 64, 65, Oct. 2010
English, Summary international conference

Cys80 of JC Virus Capsid Protein, VP1 is Essential for Intrapentamer Disulfide Bond and Pentamer Formation
Shintaro Kobayashi, Tadaki Suzuki, Manabu Igarashi, Noriko Ohtake, Keita Nagakawa, Kimihito Ito, Kenichi Niikura, Takashi Kimura, Harumi Kasamatsu, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 16, 45, 46, Oct. 2010
English, Summary international conference

ウイルスのシアル酸認識を利用した有機/無機ハイブリッドナノ粒子の構築
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 高分子学会予稿集(CD−ROM), 59, 2 Disk1, ROMBUNNO.2PC119, 01 Sep. 2010
Japanese

pHに応答した分子放出のためのウイルスナノカプセルの機能化
大竹範子, 新倉謙一, 鈴木忠樹, 三國新太郎, 松尾保孝, 永川桂太, 金城政孝, 澤洋文, 居城邦治, 日本化学会講演予稿集, 90th, 3, 888, 12 Mar. 2010
Japanese

分子シャペロン阻害剤によるTaxとTax結合蛋白質の機能相関性に対する抑制的影響
池辺詠美, 川口晶, 川口晶, 田口慎也, 川嶋太郎, 田中勇悦, 堀光雄, 澤洋文, 西園晃, 長谷川秀樹, 伊波英克, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 2010

新規エントリーレセプターを介したウマヘルペスウイルス1型の細胞内侵入機構の解析
佐々木道仁, 長谷部理絵, 福士秀人, 谷山弘行, 澤洋文, 木村享史, 日本獣医学会学術集会講演要旨集, 150th, 2010

Novel entry pathway of equine herpesvirus-1
佐々木道仁, 長谷部理絵, 澤洋文, 福士秀人, 谷山弘行, 生化学, 2010

Preparation of functionalized virus-like particles enabling pH-mediated release of target molecules
OHTAKE Noriko, NIIKURA Kenichi, SUZUKI Tadaki, MIKUNI Shintaro, MATSUO Yasutaka, NAGAKAWA Keita, KINJO Masataka, SAWA Hirofumi, IJIRO Kuniharu, Abstr RIES Hokudai Symp, 11th, 109-110, 2010
English

Inhibition of the SDF-1F?-CXCR4 Axis by the CXCR4 Antagonist AMD3100 Suppresses the Migration of Human ATLL Cells and Murine Lymphoblastoid Cells from HTLV-I Tax Transgenic Mice
A. Kawaguichi, Hidekatsu, I, H. Hasegawa, H. Sawa, M. Ogata, T. Tsuji, T. Kimura, T. Sata, W. W. Hall, Y. Orba, AIDS RESEARCH AND HUMAN RETROVIRUSES, 25, 11, 1212, 1212, Nov. 2009
English, Summary international conference

CXCR4アンタゴニスト(AMD3100)を用いたSCIDマウスにおけるTaxトランスジェニックマウス由来腫瘍細胞の組織浸潤抑制
川口晶, 辻隆裕, 大場靖子, 木村享史, 相内章, 伊波英克, 緒方正男, 佐多徹太郎, 澤洋文, 長谷川秀樹, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 445, 01 Oct. 2009
Japanese

ウイルスを中心とした金ナノ粒子の三次元配列構造体とその光学応答
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 高分子学会予稿集(CD−ROM), 58, 2 Disk1, ROMBUNNO.1L5-12, 01 Sep. 2009
Japanese

ウイルスを基盤とした金ナノ粒子の三次元配列化とその光学応答
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 高分子学会予稿集(CD−ROM), 58, 1 Disk1, 1PD088, 12 May 2009
Japanese

ウイルス様ナノカプセルを鋳型とした金ナノ粒子の3次元配列化
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 日本化学会講演予稿集, 89th, 2, 1256, 13 Mar. 2009
Japanese

Viroporin activity of JCV agnoprotein
Tadaki Suzuki, Yasuko Orba, Yuji Sunden, Takashi Kimura, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 15, 96, 97, 2009
English, Summary international conference

ヒトATL細胞及びTaxトランスジェニックマウス由来腫瘍細胞のSDF‐1αに対する走化性
川口晶, 大場靖子, 木村享史, 伊波英克, 緒方正男, 辻隆裕, 佐多徹太郎, 澤洋文, 長谷川秀樹, 日本ウイルス学会学術集会プログラム・抄録集, 56th, 247, 01 Oct. 2008
Japanese

ウイルスの糖鎖認識能を利用した金ナノ粒子の規則配列化
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 日本化学会バイオテクノロジー部会シンポジウム講演要旨集, 11th, 303, 08 Sep. 2008
Japanese

光局在場を目指したウイルスカプセル表面における金ナノ粒子の規則配列化
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 応用物理学会学術講演会講演予稿集, 69th, 3, 1218, 02 Sep. 2008
Japanese

ATL腫瘍細胞の走化性におけるCXCR4を介したシグナル経路の解析
川口晶, 大場靖子, 木村享史, 伊波英克, 緒方正男, 佐多徹太郎, 澤洋文, 長谷川秀樹, 補体シンポジウム講演集, 45th, 179, Jul. 2008
Japanese

ウイルスカプセルを鋳型とした金ナノ粒子3Dアレイの作製
永川桂大, 新倉謙一, 大竹範子, 鈴木忠樹, 松尾保孝, 澤洋文, 居城邦治, 日本化学会講演予稿集, 88th, 2, 878, 12 Mar. 2008
Japanese

ウイルスカプセルを鋳型とした金ナノ粒子3Dアレイの作製
永川桂大, 石塚範子, 新倉謙一, 松尾保孝, 鈴木忠樹, 澤洋文, 居城邦治, 高分子学会北海道支部研究発表会講演要旨集, 42nd, 21, 29 Jan. 2008
Japanese

Gab family scaffolding adaptor proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling
Yoshikazu Nakaoka, Atsunori Kamiya, Takashi Minami, Hirofumi Sawa, Yasushi Fujio, Tatsuya Koyama, Hisao Hirota, Keiko Yamauchi-Takihara, Kinya Otsu, Masatsugu Hori, Toshio Hirano, Naoki Mochizuki, CIRCULATION, 116, 16, 5, 5, Oct. 2007
English, Summary international conference

A water-soluble hsp90 inhibitor 17-DMAG suppresses tax-mediated oncogenic signaling both in vitro and in vivo
Hidekatsu Iha, Sin-ya Taguchi, Akira Kawaguchi, Taro Kawashima, Yuetsu Tanaka, Hirofumi Sawa, Akira Nishizono, Tetsutaro Sata, William Hall, Kuan T. Jeang, Hideki T. Hasegawa, AIDS RESEARCH AND HUMAN RETROVIRUSES, 23, 4, 594, 595, Apr. 2007
English, Summary international conference

The nuclear import of the HTLV-I tax protein is carrier and energy independent
Takahiro Tsuji, Noreen Sheehy, Virginie Gautier, Hitoshi Hayakawa, Hirofumi Sawa, William Hall, AIDS RESEARCH AND HUMAN RETROVIRUSES, 23, 4, 614, 614, Apr. 2007
English, Summary international conference

超分子ナノ材料としてのウイルスカプセルの作製
永川桂大, 石塚範子, 新倉謙一, 松尾保孝, 鈴木忠樹, 澤洋文, 居城邦治, 居城邦治, 高分子学会北海道支部研究発表会講演要旨集, 41st, 45, 06 Feb. 2007
Japanese

【進行性多巣性白質脳症の新しい展開 PMLが治る時代へ向けて】 JCウイルスの最近の基礎的知見　　　　　　　　　　　　　　　
澤 洋文, 鈴木 忠樹, 大場 靖子, 寸田 祐嗣, 長嶋 和郎, BRAIN and NERVE: 神経研究の進歩, 59, 2, 101, 108, Feb. 2007
(株)医学書院, Japanese

新規分子シャペロン阻害剤によるNF-κBシグナルの抑制と抗ガン剤への応用
伊波英克, 川口晶, 田口慎也, 川嶋太郎, 村上真弓, 田中勇悦, 澤洋文, 佐多徹太郎, 堀光雄, 後藤和代, 西園晃, JEANG Kuan-Teh, HALL William W, 長谷川秀樹, 生化学, 2007

Proteome analysis of Wig rat brain: A model for attention-deficit hyperactivity disorder [ADHD] research
Yoshinori Masuo, Misato Hirano, Junko Shibato, Hitoshi Iwahashi, Hirofumi Sawa, Kazuo Nagashima, Randeep Rakwal, NEUROSCIENCE RESEARCH, 58, S47, S47, 2007
English, Summary international conference

JC virus agnoprotein modifies plasma membrane permeability and facilitates
Tadaki Suzuki, Yuki Okada, Yasuko Orba, Yuji Sunden, Takashi Kimura, Kazuo Nagashima, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 128, 128, 2007
English, Summary international conference

Pharmacological cdk inhibitor suppresses JC virus proliferation
Yasuko Orba, Yuji Sunden, Tadaki Suzuki, Takashi Kimura, Shinya Tanaka, Kazuo Nagashima, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 109, 110, 2007
English, Summary international conference

Biological effects of Natalizurnab on JC virus infectivity in its permissive human neural cell lines in vitro
Tadaki Suzuki, Satoko Yamanouchi, Yuji Sunden, Yasuko Orba, Shinya Tanaka, Takashi Kimura, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 127, 127, 2007
English, Summary international conference

Visualization of West Nile virus particles for examination on the cellular entry mechanism
Yoshinori Makino, Tadaki Suzuki, Rie Hasebe, Akihiko Maeda, Hidehiro Takahashi, Takashi Kimura, Hirofumi Sawa, JOURNAL OF NEUROVIROLOGY, 13, 100, 100, 2007
English, Summary international conference

Case of highly active anti-retroviral therapy-induced immune reconstitution inflammatory syndrome in AIDS-related progressive multifocal leukoencephalopathy.　　　　　　　　　　　　　　　
Rinsho Shinkeigaku, 65, 1495, 1500, 2007

Etiological agent and pathogenicity mechanism of PML.　　　　　　　　　　　　　　　
Nippon Rinsho, 65, 1495, 1500, 2007

Recent research on the JC virus.　　　　　　　　　　　　　　　
Brain Nerve, 59, 101, 108, 2007

Pathophysiological analysis of adult T-cell Leukemia model mouse
Hall William W., 岡山実験動物研究会報, 23, 43, 44, Dec. 2006
岡山実験動物研究会, Japanese

Gab family docking proteins are essential for prevention of dilated cardiomyopathy through transmitting neuregulin-ErbB signaling
Yoshikazu Nakaoka, Keigo Nishida, Atsunori Kamiya, Hirofumi Sawa, Kinya Otsu, Hisao Hirota, Toshio Hirano, Naoki Mochizuki, JOURNAL OF CARDIAC FAILURE, 12, 8, S159, S159, Oct. 2006
English, Summary international conference

スリランカ津波被災地ならびにその近郊に生息する野生げっ歯類の病理学的検査
木村享史, 沢洋文, 片倉賢, 中村一郎, 有川二郎, 松本芳嗣, RAJAPAKSE R.P.V.Jayanthe, 高島郁夫, 梅村孝司, 日本獣医学会学術集会講演要旨集, 140th, 72, 72, 31 Aug. 2005
(公社)日本獣医学会, Japanese

Development of FRET-based probes for r-ras activation and R-Ras activation at Early/Recycling Endosomes
Akiyuki Takaya, Takahiro Kamio, Michitaka Masuda, Naoki Mochizuki, Hirofumi Sawa, Mami Satoh, Kazuo Nagashim, Akiko Mizutani, Akira Matsuno, Michiyuki Matsuda, CELL STRUCTURE AND FUNCTION, 30, 64, 64, Jun. 2005
English, Summary international conference

Development of a model of adult T-cell leukemia/lymphoma (Atll)
H Hasegawa, H Sawa, M Lewis, Y Orba, T Sata, T Kurata, K Nagashima, N Sheehy, WW Hall, AIDS RESEARCH AND HUMAN RETROVIRUSES, 21, 5, 454, 455, May 2005
English, Summary international conference

Subcellular localization of HTLV-I Tax using GFP-tagged protein
TT Tsuji, N Sheehy, H Hayakawa, Gautier, V, H Sawa, Y Okada, W Hall, AIDS RESEARCH AND HUMAN RETROVIRUSES, 21, 5, 500, 500, May 2005
English, Summary international conference

Agnoprotein plays a role in intracellular trafficking of JC virus
Hirofumi Sawa, Tadaki Suzuki, Yuki Okada, Yasuko Orba, Yuji Sunden, Shingo Semba, Kazuo Nagashima, JOURNAL OF NEUROVIROLOGY, 14, 63, 63, 2005
English, Summary international conference

A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis
Y Kamioka, S Fukuhara, M Masuda, H Sawa, K Nagashima, M Matsuda, N Mochizuki, MOLECULAR BIOLOGY OF THE CELL, 15, 79A, 79A, Nov. 2004
English, Summary international conference

JC virus agnoprotein facilitates viral propagation by removing FEZ1 from microtubules
Tadaki Suzuki, Hirofumi Sawa, Yuki Okada, Yasuko Orba, Shingo Semba, Kazuo Nagashima, JOURNAL OF NEUROVIROLOGY, 10, 131, 131, 2004
English, Summary international conference

Identification of cell surface molecule as a candidate receptor for JC virus
C. Henmi, H. Sawa, Y. Orba, S. Tanaka, K. Nagashima, JOURNAL OF NEUROVIROLOGY, 14, 42, 42, 2004
English, Summary international conference

Human polyomavirus agnoprotein disrupts the interaction between HP1 alpha and LBR
H. Sawa, Y. Okada, T. Suzuki, Y. Orba, Y. Sunden, C. Henmi, S. Semba, H. Takahashi, S. Tanaka, K. Nagashima, JOURNAL OF NEUROVIROLOGY, 14, 33, 33, 2004
English, Summary international conference

Desmoplastic malignant mesothelioma of the pleura: Autopsy reveals asbestos exposure (vol 53, pg 401, 2003)
R Ishikawa, H Kikuchi, M Jin, M Fujita, T Itoh, H Sawa, K Nagashima, PATHOLOGY INTERNATIONAL, 53, 9, 652, 652, Sep. 2003
English, Others

リアルタイムRT-PCR法を用いたJCウイルスの動態解析
山本 晋, 澤 洋文, 岩田 博司, 岡田 由紀, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 23, 90, 90, 01 May 2003
Japanese

JC virusの神経親和性を規定する転写因子
仙葉 愼吾, 長嶋 和郎, 大場 靖子, 澤 洋文, Neuropathology : official journal the Japanese Society of Neuropathology, 23, 202, 202, 01 May 2003
Japanese

siRNAを用いたJC virus関連蛋白質の発現抑制
大場 靖子, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 23, 201, 201, 01 May 2003
Japanese

JCウイルス外郭蛋白質VP1は糖脂質と糖蛋白質の糖鎖に結合する
澤 洋文, 駒込 理佳, 田中 伸哉, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 23, 199, 199, 01 May 2003
Japanese

Parkinsonism、顔面・体幹・四肢近位優位の筋萎縮を呈する神経原性筋萎縮症
長嶋 淑子, 島 功二, 中馬 孝容, 真野 行生, 後藤 雄一, 西野 一三, 埜中 征哉, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 23, 315, 315, 01 May 2003
Japanese

糖尿病・腎不全の高齢透析患者に生じた亜急性代謝性脳症
長嶋 淑子, 岩崎 素之, 北村 淳, 寺坂 俊介, 布村 充, 高田 珠, 滝沢 英樹, 村上 弘則, 中馬 孝容, 真野 行生, 後藤 雄一, 西野 一三, 埜中 征哉, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 23, 0, 305, 305, 01 May 2003
Japanese

The human polyomavirus Jc induces chromosomal instability in colonic cells
L Ricciardiello, M Baglioni, MP Landini, A Ripalti, H Sawa, K Nagashima, RJ Frisque, A Goel, CR Boland, M Tognon, E Roda, F Bazzoli, GASTROENTEROLOGY, 124, 4, A603, A603, Apr. 2003
English, Summary international conference

An atypical form of sporadic panencephalopathic Creutzfeldt-Jakob disease in Japan [1]
S. Yamamoto, H. Furukawa, T. Kitamoto, Y. Takamaru, N. Morita, M. Yasuda, Y. Okada, H. Sawa, K. Nagashima, Neuropathology and Applied Neurobiology, 29, 1, 77, 80, Feb. 2003
English, Report scientific journal

Advanced glycation end products induce angiogenesis in vivo
AC Stan, T Okamoto, S Tanaka, T Koike, M Kase, Z Makita, H Sawa, K Nagashima, ACTA NEUROPATHOLOGICA, 104, 5, 570, 570, Nov. 2002
English, Summary international conference

Expression of JC virus agnoprotein in progressive multifocal leukoencephalopathy brain
AC Stan, Y Okada, H Sawa, S Endo, Y Orba, T Umemura, H Nishihara, S Tanaka, H Takahashi, K Nagashima, ACTA NEUROPATHOLOGICA, 104, 5, 570, 570, Nov. 2002
English, Summary international conference

Differential requirement for Apaf1 and Bcl-X-L in the regulation of programmed cell death during development
H Yoshida, Y Okada, N Kinoshita, H Hara, M Sasaki, H Sawa, K Nagashima, TW Mak, K Ikeda, N Motoyama, CELL DEATH AND DIFFERENTIATION, 9, 11, 1273, 1276, Nov. 2002
English, Report scientific journal

シグナル伝達アダプター分子CrkによるERMの局在変化と細胞運動能及び接着能の解析
津田真寿美, 田中伸哉, 牧野吉倫, 西原広史, 沢洋文, 長嶋和郎, 日本癌学会総会記事, 61st, 317, 25 Aug. 2002
Japanese, Others

JCウイルスからみたグリアの生物科学 (特集 グリアの生物科学)
仙葉 愼吾, 澤 洋文, 長嶋 和郎, 神経研究の進歩, 46, 4, 557, 565, Aug. 2002
医学書院, Japanese

関節拘縮・硬直脊椎・CK著高を伴うdysferlin欠損肢体型筋ジストロフィー(LGMD2B)の1例
長嶋 淑子, 山口 康一, 村上 浩則, 篠原 敦也, 中馬 孝容, 真野 行生, 後藤 雄一, 南 成祐, 埜中 征也, 河合 祥雄, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 22, 184, 184, 01 May 2002
Japanese

神経症状から診断されたSjogren症候群の臨床病理学的検討
長嶋 淑子, 滝沢 昌彦, 間口 四郎, 佐々木 勲, 篠原 敏也, 大場 靖子, 中馬 孝容, 真野 行生, 澤 洋文, 長嶋 和郎, 酒井 宏一郎, Neuropathology : official journal the Japanese Society of Neuropathology, 22, 50, 50, 01 May 2002
Japanese

遺伝子導入ベクターとしてのJC virus(JCV)VP1の有用性
逸見 千寿香, 岩田 博司, 駒込 理佳, 佐藤 真実, 田中 伸哉, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 22, 52, 52, 01 May 2002
Japanese

進行性多巣性白質脳症(PML)におけるJC virus Agnoproteinの発現と局在
大場 靖子, 岡田 由紀, 遠藤 秀一, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 22, 49, 49, 01 May 2002
Japanese

アダプター分子v‐CrkによるRho依存的細胞骨格制御と細胞運動能の解析
津田真寿美, 田中伸哉, 西原広史, 沢洋文, 長嶋和郎, 日本病理学会会誌, 91, 1, 159, 28 Feb. 2002
Japanese, Others

Laser capture microdissection法を用いた胆汁細胞診標本からの細胞採取とK‐ras遺伝子変異の検索
大場靖子, 西原広史, 田中伸哉, 沢洋文, 伊藤智雄, 長嶋和郎, 日本病理学会会誌, 91, 1, 298, 28 Feb. 2002
Japanese, Others

Molecular Neuropathology of JC Virus
大場 靖子, 澤 洋文, 長嶋 和郎, Brain and nerve : 神経研究の進歩, 54, 2, 101, 109, Feb. 2002
医学書院, Japanese

DNA polymerase Λ(β2). Analysis of the mechanism of the hydrocephalus crisis in the knockout mouse and analysis of the gene abnormality in the hydrocephalus DNA bank(Ministry of Health, Labour and Welfare S).
小林洋介, 渡部美穂, 岡田由紀, 沢洋文, 鈴木宏志, 金村米博, 山崎麻美, 長嶋和郎, 本山昇, 先天性水頭症の分子生物学的メカニズム解明と治療法開発に関する研究 平成13年度総括・分担研究報告書, 2002

Chk2ノックアウトマウスにおける自然発癌の解析
岡田由紀, 沢洋文, 高井裕之, 原田直樹, 門内有美, 渡部美穂, 長嶋和郎, 池田恭治, 本山昇, 日本癌学会総会記事, 61st, 2002

DNA PolymeraseλKOマウスはKartagener症候群類似の病態を示す　　　　　　　　　　　　　　　
小林 洋介, 渡部 美穂, 岡田 由紀, 高井 裕之, 澤 洋文, 鈴木 宏志, 中西 真, 長嶋 和郎, 池田 恭治, 本山 昇, 日本臨床分子医学会学術総会プログラム・抄録集, 38回, 59, 59, Aug. 2001
日本臨床分子医学会, Japanese

Broad distribution of the JC virus receptor contrasts with a marked cellular restriction of virus replication
S Suzuki, H Sawa, R Komagome, Y Orba, M Yamada, Y Okada, Y Ishida, H Nishihara, S Tanaka, K Nagashima, VIROLOGY, 286, 1, 100, 112, Jul. 2001
English

JC virus large T protein transforms rodent cells but is not involved in human medulloblastoma
H Hayashi, S Endo, S Suzuki, S Tanaka, H Sawa, Y Ozaki, Y Sawamura, K Nagashima, NEUROPATHOLOGY, 21, 2, 129, 137, Jun. 2001
English

HHV8-negative primary effusion lymphoma of the peritoneal cavity presenting with a distinct immunohistochemical phenotype
S Tanaka, H Katano, K Tsukamoto, M Jin, S Oikawa, H Nishihara, H Sawa, K Sawada, M Shimizu, T Sata, Y Fujioka, K Nagashima, PATHOLOGY INTERNATIONAL, 51, 4, 293, 300, Apr. 2001
English

滑膜肉腫の癌化機構におけるSYT‐SSX1キメラ蛋白の役割
長井真人, 田中伸哉, 平賀博明, 津田真寿美, 遠藤秀一, 沢洋文, 西原広史, 長嶋和郎, 日本病理学会会誌, 90, 1, 190, 01 Mar. 2001
Japanese, Others

すい癌におけるSykの発現の検討 浸潤・転移への関与について
渡辺佳明, 西原広史, 田中伸哉, 沢洋文, 清水道生, 長嶋和郎, 日本病理学会会誌, 90, 1, 292, 01 Mar. 2001
Japanese, Others

JC virus(JCV) agnoproteinの発現と機能に関する研究
岡田由紀, 沢洋文, 遠藤秀一, 大場靖子, 西原広史, 田中伸哉, 長嶋和郎, 日本病理学会会誌, 90, 1, 349, 01 Mar. 2001
Japanese, Others

Familial HTLV-I associated polyneuropathy
T Nagashima, N Shinmyo, T Chuma, Mano, I, Y Okada, H Sawa, K Nagashima, AIDS RESEARCH AND HUMAN RETROVIRUSES, 17, S64, S64, 2001
English, Summary international conference

Neural cell specific activation of the JC virus promoter in the presence of HTLV-1 Tax.
Y Okada, H Sawa, S Tanaka, S Suzuki, H Hasegawa, WW Hall, K Nagashima, AIDS RESEARCH AND HUMAN RETROVIRUSES, 17, S56, S56, 2001
English, Summary international conference

Semi-Quantitative RT-PCR analysis of Rat Brain in Methylmercury Intoxication.
NAGASHIMA KAZUO, OIDA KENJI, NISHIHARA HIROSHI, TANAKA SHIN'YA, SAWA HIROFUMI, 有機水銀の健康影響に関する研究 平成12年度 重金属等の健康影響に関する総合研究班, 3-8, 2001
Japanese, Others

浮遊細胞特異的に発現するCDM‐family蛋白 DOCK2の機能の解析
前田才恵, 西原広史, 田中伸哉, 松田道行, 沢洋文, 長嶋和郎, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 432, 25 Nov. 2000
Japanese, Others

ヒト滑膜肉腫関連蛋白SYT‐SSX1とクロマチンリモデリング因子hBRMの結合の機能解析
長井真人, 田中伸哉, 津田真寿美, 園部宏, 加藤宏幸, 平賀博明, 西原広史, 沢洋文, 長嶋和郎, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 338, 25 Nov. 2000
Japanese, Others

Expression of JC virus early and late proteins in various cell lines and PML brains
H Sawa, Y Okada, S Tanaka, Y Orba, S Endo, M Sasada, Y Hara, M Shintaku, K Nagashima, BRAIN PATHOLOGY, 10, 4, 757, 757, Sep. 2000
English, Summary international conference

腫よう組織における前癌遺伝子産物CRKの発現と細胞増殖能に関する分子病理学的解析
西原広史, 田中伸哉, 清水道生, 沢洋文, 松田道行, 長嶋和郎, Jpn J Cancer Res, 91, Supplement (Sept), 499, 01 Sep. 2000
Japanese, Others

ヒト滑膜肉腫関連SYT‐SSX1遺伝子の形質転換機構
長井真人, 田中伸哉, 沢洋文, 西原広史, 津田真寿美, 長嶋和郎, Jpn J Cancer Res, 91, Supplement (Sept), 53, 01 Sep. 2000
Japanese, Others

JC virus 構成蛋白の発現と機能に関する研究
岡田 由紀, 遠藤 秀一, 原 由紀子, 大場 靖子, 駒込 理佳, 田中 伸哉, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 20, 59, 59, 01 Jun. 2000
Japanese

Dendritic distribution of JC virus agnoprotein in PML brain.
K Nagashima, H Sawa, Y Ohba, S Endo, Y Okada, S Tanaka, JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 59, 5, 427, 427, May 2000
English, Summary international conference

DNA polymerase β2欠損マウスは出生後の発育遅延及び水頭症を呈する
小林洋介, 渡部美穂, 高井裕之, 岡田由紀, 沢洋文, 鈴木宏志, 中西真, 池田恭治, 本山昇, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 2000

daf-16のほ乳類ホモログAFX,FKHR,FKHRL1の機能解析
吉田聖美, 岡田由紀, 沢洋文, 池田恭治, 本山昇, 日本分子生物学会年会プログラム・講演要旨集, 23rd, 2000

HTLV-I TaxによるJC virusの活性化に関する研究
岡田 由紀, 澤 洋文, 田中 伸哉, 伊藤 智雄, 長谷川 秀樹, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 19, 69, 69, 03 Jun. 1999
Japanese

0499 新しい高周波広域地域探触子による血管外からの冠動脈の観察
山田 聡, 西原 馨子, 齋藤 尚孝, 小野塚 久夫, 北畠 顕, 澤 洋文, 長嶋 和郎, 三神 大世, Japanese circulation journal, 63, 1, 274, 274, 01 Mar. 1999
社団法人日本循環器学会, Japanese

Cloning of a novel matrix metalloproteinase specifically expressed in femal reproductive tracts
OHNISHI Junji, HIRANO Wakako, NAKANE Dai, MATSUI Hitoshi, KIMURA Atsushi, SAWA Hirofumi, NAGASHIMA Kazuo, TAKAHASHI Takayuki, 日本分子生物学会年会プログラム・講演要旨集, 21, 677, 677, 01 Dec. 1998
Japanese

進行性多巣性白質脳症とJCウイルス調節領域
澤 洋文, 古林 与志安, 平賀 博明, 田中 伸哉, 涌谷 陽介, 松本 理器, 森 雅裕, 余郷 嘉明, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 18, 182, 182, 28 May 1998
Japanese

Distributional pattern of apoptotic cells in rat cerebellar vermis experimentally induced by methylmercury intoxication
Y Kobayashi, H Sawa, H Akagi, C Itakura, Y Fujioka, K Nagashima, NEUROPATHOLOGY, 18, 1, 33, 37, Mar. 1998
English

0822 拡張型心筋症におけるオステオポンチンの心筋線維化への関与
渡邊 正司, 岡本 洋, 千葉 知, 熊本 秀樹, 中川 泉, 米谷 圭史, 小野塚 久夫, 北畠 顕, 川口 秀明, 三神 大世, 澤 洋文, Japanese circulation journal, 62, 311, 311, 28 Feb. 1998
社団法人日本循環器学会, Japanese

Molecular cloning and characterization of a novel target of H-ras protein which belongs to RalGDS family
N Mochizuki, T Murakami, N Makita, H Sawa, GR Post, CIRCULATION, 96, 8, 3112, 3112, Oct. 1997
English, Summary international conference

有機水銀投与ラットでみられる小脳顆粒細胞アポトーシスの分布とアポトーシス関連蛋白/遺伝子の解析
古林 与志安, 澤 洋文, 赤木 洋勝, 板倉 智敏, 藤岡 保範, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 17, 149, 149, 26 May 1997
Japanese

0801 Urokinase type plasminogen activator受容体(uPAR)を強制発現させた内皮細胞における線溶系の亢進
澤 洋文, 藤井 聡, 北畠 顕, Japanese circulation journal, 61, 313, 313, 05 Mar. 1997
社団法人日本循環器学会, Japanese

1036 Plasminogen activator inhibitor-1(PAI-1)に対するアンチセンスオリゴヌクレオチドによるballoon injury後の内膜肥厚の抑制
澤 洋文, 藤井 聡, 北畠 顕, Japanese circulation journal, 61, 372, 372, 05 Mar. 1997
社団法人日本循環器学会, Japanese

Expression of amyloid precursor protein mRNA in vascular smooth muscle cells of the human brain
RH Takahashi, H Sawa, A Takada, A Kitabatake, K Nagashima, NEUROPATHOLOGY, 17, 1, 11, 14, Mar. 1997
English

Pathologic processes leading to cerebral hemorrhage in amyloid angiopathy
RH Takahashi, H Sawa, S Kuroda, H Saito, M Fujita, Y Fujioka, R Fukatsu, K Nagashima, NEUROPATHOLOGY, 16, 2, 99, 105, Jun. 1996
English

新発色基質であるHNPPの神経疾患解析への応用 : FISH法、免疫染色法、in situ hybridization法の検討
佐藤 真実, 高橋 文誉, 大場 靖子, 近藤 恭光, 鍵山 直人, 高橋 礼典, 澤 洋文, 長嶋 和郎, Neuropathology : official journal the Japanese Society of Neuropathology, 16, 203, 203, 01 May 1996
Japanese

Expression of vascular endothelial growth factor in human myocardial infarction
K Shinohara, T Shinohara, N Mochizuki, Y Mochizukik, H Sawa, T Kohya, M Fujita, Y Fujioka, A Kitabatake, K Nagashima, HEART AND VESSELS, 11, 3, 113, 122, 1996
English

SLEにおける肺高血圧症(PH)合併例の臨床的検討 : 日本循環器学会第62回北海道地方会
山田 豊, 遠藤 由香, 布施川 哲, 西島 宏隆, 小林 毅, 安田 寿一, 沢 洋文, 長嶋 和郎, Japanese circulation journal, 57, 492, 492, 20 May 1993
社団法人日本循環器学会, Japanese

EXPRESSION OF THE RENIN GENE AND LOCALIZATION OF ITS PROTEIN IN THE HUMAN HEART
Y ENDO, N MOCHIZUKI, H SAWA, A TAKADA, Y FURUTA, F TOKUCHI, K SHINOHARA, T SHINOHARA, H KAWAGUCHI, A KITABATAKE, K NAGASHIMA, CIRCULATION, 86, 4, 349, 349, Oct. 1992
English, Summary international conference

2度の急性心筋梗塞を合併した肥大型心筋症の1例(日本循環器学会 第64回北海道地方会)
横式 尚司, 米田 恵理子, 岡田 斉, 澤 洋文, 三神 大世, 小林 毅, 安田 寿一, 藤岡 保範, 長嶋 和郎, Japanese circulation journal, 56, 711, 711, 20 Jul. 1992
社団法人日本循環器学会, Japanese

EXPRESSION OF THE ANGIOTENSINOGEN GENE AND LOCALIZATION OF ITS PROTEIN IN THE HUMAN HEART
H SAWA, F TOKUCHI, N MOCHIZUKI, Y ENDO, Y FURUTA, T SHINOHARA, A TAKADA, H KAWAGUCHI, H YASUDA, K NAGASHIMA, CIRCULATION, 86, 1, 138, 146, Jul. 1992
English

ラット圧負荷モデルにおける心臓でのレニン, アンジオテンシノーゲンmRNAの発現について
遠藤 由香, 望月 直樹, 澤 洋文, 川口 秀明, 安田 寿一, 篠原 敏也, 古田 康, 高田 明生, 長嶋 和郎, Japanese circulation journal, 56, 397, 397, 01 Mar. 1992
社団法人日本循環器学会, Japanese

PHOSPHATIDYLINOSITOL AND INOSITOLPHOSPHATIDE METABOLISM IN HYPERTROPHIED RAT HEART
SHOKI MIKAKO, KAWAGUCHI HIDEAKI, OKAMOTO HIROSHI, SANO HITOSHI, SAWA HIROFUMI, KUDO TOSHIYUKI, HIRAO NORIFUMI, SAKATA YOSHIHITO, YASUDA HISAKAZU, Japanese circulation journal, 56, 2, 142, 147, 20 Feb. 1992
The accumulation of both Inositol-(1,4,5)-trisphosphate (IP_3) and Inositol-(1,3,4,5)-tetrakisphosphate (IP_4) after hormonal stimulation has a physiological role, possibly in altering Ca^<2+> levels in cardiac tissue. However, the accumulation of inositol polyphosphate under pathophysiological conditions has not been studied. In our experiments the metabolism of phatidylinositol and IP_3 m cardiac myocytes as investigated. It was shown that basal levels of cytosolic phosphatidylinositol specific phospholipase C (PI-PLC), phosphatidylinositol-(4,5)-bisphosphate specific phospholipase C (PIP_2-PLC) activities markedly increased in stroke-prone spontaneously hypertensive rats (SHRSP) with age compared with age matched Wistar Kyoto rats (WKY). IP_3 kinase and IP_3 phosphatase activities also increased in SHRSP hearts with age. Their activities increased in WKY, but to a lesser antent than in SHRSPs. These data suggest that a PI turnover pathway such as the phosphatidylinositol 4,5-bisphosphate-IP_3-Ca^<2+> pathway or the diacylglyceride-protein kinase C pathway may have an important role in the development of hypertrophy in SHRSP heart., Japanese Circulation Society, English

DETECTION OF HUMAN PAPILLOMAVIRUS DNA IN CARCINOMAS OF THE NASAL CAVITIES AND PARANASAL SINUSES BY POLYMERASE CHAIN-REACTION
Y FURUTA, T TAKASU, T ASAI, T SHINOHARA, H SAWA, K NAGASHIMA, Y INUYAMA, CANCER, 69, 2, 353, 357, Jan. 1992
English

-1154-IMMUNOHISTOCHEMICAL STUDY OF ANP-C Rc(CLEARANCE RECEPTOR) : THE 54th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY
MOCHIZUKI Naoki, SAWA Hirofumi, YASUDA Hisakazu, NAGASHIMA Kazuo, HIROSE Shigehisa, Japanese circulation journal, 54, 8, 1047, 1047, 20 Aug. 1990
Japanese Circulation Society, English

-0078-THE MECHANISM OF INCREASED ANGIO TENSIN CONVERTING ENZYME ACTIVITY STIMULATED WITH PLATELET ACTIVATING FACTOR
Kawaguchi Hideaki, Sawa Hirofumi, Yasuda Hisakazu, Japanese circulation journal, 54, 7, 719, 719, 20 Jul. 1990
Japanese Circulation Society, English

-345-LOCALIZATION OF ATRIAL NATRIURETIC PEPTIDE IN HUMAN VENTRICULAR SYSTEM : Atrial Natriuretic Polypeptide : FREE COMMUNICATIONS(II) : PROCEEDINGS OF THE 53th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY
Sawa Hirofumi, Mochizuki Naoki, Kawaguchi Hideaki, Yasuda Hisakazu, Sano Kimiaki, Shinohara Toshiya, Nagashima Kazuo, Japanese circulation journal, 53, 6, 579, 579, 20 Jun. 1989
Japanese Circulation Society, English

プリオン病と遅発性ウイルス感染症　　　　　　　　　　　　　　　
金原出版, 2010

Molecular Biology of Tumor Virus Gene Products.　　　　　　　　　　　　　　　
Research Signpost, 2009

DNA viruses, Methods and Protocols.　　　　　　　　　　　　　　　
Humana Press, 2005

Understanding of Minamata disease. Methylmercury poisoning in Minamata and Niigata, Japan　　　　　　　　　　　　　　　
Japan Public Health Association, 2001

Endokrine und zellbiologische aspekte der arteriosklerose 10　　　　　　　　　　　　　　　
Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung, 1996

Arteriosklerose zerebraler gefäß 9　　　　　　　　　　　　　　　
Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung, 1995

Elucidation of the mechanism of developmental abnormalities caused by oropouche virus infection using animal models
Grants-in-Aid for Scientific Research
01 Apr. 2025 - 31 Mar. 2028
澤 洋文, 板倉 友香里, 松野 啓太
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 25K09431

The role of MHC class I transactivator NLRC5 in COVID-19
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2025
小林 弘一, 澤 洋文, 福原 崇介, 應田 涼太
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 22H02883

VIrome analysis of bats in Indonesia
Grants-in-Aid for Scientific Research
01 Apr. 2021 - 31 Mar. 2024
澤 洋文, 大場 靖子, 佐々木 道仁
コウモリは人に致死的な肺炎、出血熱、脳炎、狂犬病 等の自然宿主と考えられている。現在の国際社会のCOVID-19の感染状況において、飛行機等による交通は制限されており、出入国の際には検疫が必要である。斯かる状況において、私達が海外において疫学活動を実施し、コウモリの検体を入手すること、および、海外からコウモリの検体を日本に輸送することは極めて困難である。
そこで本研究計画では、申請者の所属する研究施設に保管されているインドネシアのコウモリから採集した検体を使用することによって、海外に渡航する困難を克服できる。コウモリは3つの島 （スマトラ、ジャワ、スラウェシ）から採集しており、インドネシア地域でのウイルスの多様性を確認することが可能である。多くのウイルスの自然宿主であるコウモリにおいて、新規・既知のウイルスの存在を明らかにすることを計画する。公衆衛生学的に重要と考えられるコウモリ由来のウイルスの存在を明らかにすることを本研究の目的とする。
令和4年度においては我々の研究グループが2010年から2014年にかけて、スマトラ、ジャワ、スラウェシで採集したコウモリを対象とし血清(133検体）、糞便(96検体）および肺（172検体）を用いて、ネルソンベイオルソレオウイルスの血清疫学調査、ゲノムの検出、ウイルスの単離を試みた。その結果、血清(133検体）の内119検体で中和抗体が陽性であること、nested RT-PCR法を用いて、糞便96検体中6検体からウイルスゲノムを検出した。肺172検体からはゲノムは検出出来なかった。さらに、ゲノムが陽性であった糞便検体を、ウイルス感染を増強させることを目的として、セリンプロテアーゼであるTMPRSS2を強制発現させたVero細胞に接種してウイルスを単離した。最終的に単離したウイルスゲノムの分子系統学的解析、細胞での増殖の解析、マウスへの病原性の解析を実施した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 21K05951

「ネオウイルス学」の国際活動支援
科学研究費助成事業
30 Jun. 2016 - 31 Mar. 2023
河岡 義裕, 朝長 啓造, 澤 洋文, 高橋 英樹, 川口 寧, 渡辺 登喜子, 松浦 善治, 鈴木 信弘, 長崎 慶三
国際活動支援班では、各研究班の海外における研究活動を促進するために、 (1) 国際研究ネットワークの整備および強化、(2) 円滑な海外での研究試料の採取支援・提供、(3) 国際シンポジウムの開催および海外研究者の招聘による人的連携の促進、(4) サンプル収集のための海外への研究者の派遣の支援、(5) 最先端研究を行う先進諸国への若手研究者の中長期的派遣の支援、(6) 国際研究者ネットワークへの積極的な情報発信を行なっている。
2021年度は、国内で国際学会を1回 [第19回あわじ感染と免疫国際フォーラム]を共催し、また、同学会の直後に国際シンポジウムを主催した。これらの学会およびシンポジウムを通じて、海外から総計12名の研究者をオンライン招聘したほか、班員12名が発表した。招聘した研究者と計画研究班、および公募研究班班員はオンライン交流を通じて人的連携を構築した。また、引き続き、本領域のホームページの英語版を通して国際社会に本領域の活動を発信している。
COVID-19の感染拡大により、海外へサンプル収集に行くことが困難な状況であったため、海外からのサンプル輸入、および海外で採取したサンプルのネオウイルス学的解析、国内で採取したサンプルの解析結果との比較解析のための支援を実施した。
日本学術振興会, 新学術領域研究(研究領域提案型), 東京大学, 16K21723

ネオウイルス学：生命の源流から超個体、そしてエコ・スフィアーへ
科学研究費助成事業
01 Apr. 2021 - 31 Mar. 2022
河岡 義裕, 朝長 啓造, 澤 洋文, 松浦 善治, 川口 寧, 渡辺 登喜子, 鈴木 信弘, 高橋 英樹, 長崎 慶三
「ネオウイルス学」領域内の計画研究および公募研究で得られた各班それぞれの研究テーマについて研究成果を取りまとめ、さらに班間、あるいは、「共進化」、「共生」、「多様性」ユニット間の連携テーマの重要性・意義を考慮しつつ、領域全体の研究成果を取りまとめた。業績集を作成し、冊子体として印刷して領域内外で配布することによって、本領域の研究成果を発信した。報告内容は、出来るだけ分かりやすい記述を心がけ、学術分野だけでなく、一般国民にも読んでもらえるような業績集を作成した。また、高校生、大学生、一般の国民に向けた講演会やセミナー、そして領域ホームページとTwitterによって、領域の活動内容や研究成果を報告することによって、国民に向けた研究成果の発信に努めた。また、新しい試みとして「ウイルスおりがみ」を作成した。ウイルスおりがみは、おりがみを折ることで、一般国民にウイルスの面白さを知ってもらうことを目的とした、科学コミュニケーションツールであり、公募研究班の牧野晶子助教（京都大）、デザイン・ユニットCOCHAE、合同会社SHIBUYA PUBLISHING & BOOKSELLERS、三宅文子アート・プランナーらのグループによって作成された。ウイルスおりがみには領域内の研究者による解説も加えられており、ウイルスの基本、構造の面白さ、役に立つウイルス、生き物の中にいる多様なウイルスについて学ぶことができる。ウイルスおりがみの配布の公募をしたところ2288部の応募があり、抽選で500部を無償で配布した。日本デザイン振興会が主催するグッドデザイン賞へウイルスおりがみを出品中である。
日本学術振興会, 新学術領域研究(研究領域提案型), 東京大学, 21H00456

Comprehensive investigation and functional analysis of endogenous viruses and endogenous viral elements in hematophagous arthropods and their host animals
Grants-in-Aid for Scientific Research
30 Jun. 2016 - 31 Mar. 2021
Sawa Hirofumi
Blood-sucking arthropods, such as mosquitoes and ticks, have been studied as vectors of pathogens, including zoonotic viruses.
In this study, we examined especially endogenous viruses in ticks and mosquitoes and investigated their roles in nature under the “dance floor” hypothesis; in blood-sucking arthropods, their indigenous microorganisms and those from human or animal blood are communicating each other.
As a result, we have discovered new endogenous viruses in the mosquitoes and ticks collected worldwide and found that these viruses may have co-evolved with their hosts.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 16H06431

Neo-virology: the raison d'etre of viruses
Grants-in-Aid for Scientific Research
30 Jun. 2016 - 31 Mar. 2021
Kawoaka Yoshihiro
We have established a new academic field, designated as ‘Neo-virology’, in which we define a virus as a component of the global ecosystem and aim to elucidate its key roles in host organisms and the global ecosystem. We have constructed a system to support research activities, facilitate collaborations among research groups, develop human resources, plan and manage scientific meetings, and support public relations activities, all of which have resulted in accelerating this new field of research. Our efforts have produced numerous noteworthy publications and have helped develop many young investigators, who will continue the growth of Neo-Virology into the future.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), The University of Tokyo, 16H06429

Investigation of latent pathogenic viruses in Latin America and South-eastern Asia by virome analysis
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2020
Sawa Hirofumi
We obtained results based on three projects that aimed at; 1) Implementing epidemiological research in Latin America and South-eastern Asia, 2) Analysis of viral genome using “Virome methods”, 3) Investigation of distribution, evolution and the infection cycle of viruses.
During screening of mosquito and fruit bat samples collected in Latin America and South-eastern Asia, respectively, we detected novel viruses i.e. flaviviruses from mosquitoes and gammaherpesviruses from fruit bats. Furthermore, we performed Virome analysis using pooled fecal samples obtained from 50 non-human primates, from which we isolated a new small circular replication-associated protein (Rep) encoding single-stranded (CRESS) DNA viruses. Additionally, genome analysis of the polyomaviruses isolated from several different horseshoe bats indicated evidence of ‘host-switching’ during evolution in horseshoe bats.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16H05805

Functional analysis of equine herpesvirus-1 receptor and its application for infection prevention
Grants-in-Aid for Scientific Research
2008 - 2011
KIMURA Takashi, SAWA Hirofumi
We analyzed the function of equine MHC class I molecule A68, which was cloned from an equine brain microvascular endothelial cell cDNA expression library as an EHV-1 receptor. Studies suggest that equine MHC class I is a functional gD receptor that plays a pivotal role in EHV-1 entry into equine cells, and also suggest that the amino acid residue at position 173 of the MHC class I molecule is involved in the efficiency of EHV-1 entry. In addition, we generated transgenic mice expressing A68, and also evaluated the usefulness of soluble forms of A68 molecules for preventing EHV-1 infection.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20380165

ウイルスを鋳型とした金属微粒子3次元規則配列構造の構築
科学研究費助成事業
2007 - 2008
新倉 謙一, 澤 洋文, 松尾 保孝, 居城 邦治
ウイルスのタンパク質が自己集合して形成するウイルス様微粒子(virus-like particle : VLP)は、ウイルスゲノムを持たずにウイルスと同じ経路で細胞内へ導入されるため、ドラッグデリバリーシステムのキャリアー等として注目されている。私たちはVLPの持つ糖鎖認識性に着目し、糖鎖の分子認識を利用してウイルスの周辺に規則的に金属微粒子を配列させることを目的に研究を進めた。まず金微粒子にシアル酸を提示させる技術を確立した。このシアル酸提示金微粒子は非常に水への分散性が高く、ウイルスと結合させても沈殿するようなことはなかった。VLPとシアル酸を修飾した金ナノ粒子の複合体形成の電子顕微鏡像(STEM)を詳細に検討すると、VLPの表層に特異的に金ナノ粒子が結合している様子が観察された。また、紫外可視吸収スペクトルの長波長シフトには、金ナノ粒子表面のシアル酸の有無によって有意な差が生じたことから、溶液中でも金ナノ粒子がVLPに結合していることが示された。さらに金ナノ粒子濃度の上昇に伴いプラズモン吸収の長波長側への大きなシフトが測定された。これはウイルスを鋳型とした金ナノ粒子の結合により、三次元的なプラズモンのカップリングが起きたことを意味している。さらにウイルスと金微粒子の結合を促進するために、デキストランを添加した。この効果は高分子クラウディング効果と言われるが、金属微粒子と生体分子(この場合はVLP)の特異的な結合をクラウディング効果で成功させた初めての例である。本研究によってウイルス-金微粒子複合体が外部の光と共鳴するプラズモン共鳴体になりうることを証明できた。
日本学術振興会, 萌芽研究, 北海道大学, 19655058

Investigations for new pathogeneses of sudden deafness and Bell's palsy
Grants-in-Aid for Scientific Research
2007 - 2008
FURUTA Yasushi, ORIDATE Nobuhiko, TAKEICHI Norihito, SAWA Hirofumi
原因不明の内耳疾患であるBell麻痺・突発性難聴において、発症時の患者の生体反応を遺伝子・蛋白質レベルで網羅的に捉えることにより、これら疾患における発症病態・新規病因を解明することを目的とし研究をおこなった。その結果、Bell麻痺においては自然免疫に関与する抗菌性小ペプチドであり、抗ウイルス作用を有することが判明しているα-defensinがベル麻痺の発症に関与していることが推定された。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 19591949

Analysis of West Nile virus neuroinvasion using in vitro blood-brain barrier models
Grants-in-Aid for Scientific Research
2006 - 2007
KIMURA Takashi, YOSHII Kentaro, SAWA Hirofumi
1. The pathway used by West Nile virus (WNV) to leave the bloodstream and invade the central nervous system is poorly understood. To investigate how WNV cross the blood-brain barrier (BBB), we used confluent human umbilical vein endothelial cells (HUVEC) cultures on transwell inserts as an in vitro BBB model.
2. The structural protein genes (C-PrM-E region) of WNV 6-LP strain and Eg 101 strain were cloned into the pCMV expression vector. Sequential transfection of WNV sub-genomic replicon having an EGFP expression cassette and the vector that expressed the structural proteins led to the secretion of virus-like particles (VLPs). VLPs established a single-round of infection without production of progeny, and the physical structure of the VLPs was similar to that of infectious virions.
3. In vitro BBB model was infected with VLPs having structural proteins of high vilulent 6LP strain (6LP-VLPs) or VLPs having structural proteins of low vilurent Eg 101 strain (Eg-VLPs). By 24 h after infection, 10% of 6LP-VLPs had crossed in vitro BBB, whereas no Eg-VLPs seemd to traverse. Thus, the ability of WNV to cross BBB may correlate at least in part with viral virulence. Exposure of HUVEC to 6LP strain did not alter the localization of tight junction protein ZO-1, indicating that the passage of WNV across the BBB is not caused by the disruption of tight junction. On the other hand, infection of HUVEC with 6LP strain was inhibited by Chlorpromazine, an inhibitor of clathrin-coated pit formation at the plasma membrane. These results suggest the possibility that WNV may cross BBB by transcytosis via a clathrin-mediated endocytic pathway.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 18580302

Investigation on the pathogenesis of herpetic facial nerve paralysis
Grants-in-Aid for Scientific Research
2004 - 2006
FURUTA Yasushi, SAWA Hirofumi, NAKAMARU Yuji
1,Patterns of herpes virus reactivation in facial nerve paralysis
We analyzed the relationship between HSV-1NZV load and onset of facial paralysis in patients with facial paralysis. The results indicate that facial paralysis can occur at various times between the early and the regression phase of HSV-1NZV reactivation, suggesting that there are variable patterns of development of facial nerve dysfunction caused by herpes virus reactivation and the progression of neuritis.
2,Gene expression analysis in patients with Bell's palsy
Gene expression profile was analyzed in patients with Bell's palsy using DNA microarray. We found several genes which were up-or down-regulated at the onset of Bell's palsy.
3,Analysis of patients with Bell's palsy who showed incomplete recovery
This study analyzed the causes of clinically diagnosed Bell's palsy who showed incomplete recovery of facial movement. The results indicate that VZV or HSV-1 reactivation is the major cause of Bell's palsy with poor prognosis.
4, Prevalence of HSV-1 reactivation in acute peripheral facial paralysis
We analyzed the prevalence of HSV-1 reactivation in acute facial paralysis. The results suggested that in clinically diagnosed Bell's palsy 20% have ZSH and 20% have non-HSVNZV palsy, and the remaining 60% might have HSV-1 related palsy.
5, Efficacy of anti-viral therapy in herpetic facial nerve paralysis
This study analyzed the HSV-1NZV load to assess the efficacy of the anti-viral therapy in patients with herpetic facial nerve paralysis. Anti-viral therapy may not be effective in all patients with HSV-1NZV reactivation because the facial paralysis can occur at various times between the early and the regression phase of HSV-1/VZV reactivation.
6, Assessments of the botulinum toxin therapy for synkinesis after facial palsy
We have treated 17 patients with facial synkinesis after herpetic facial palsy with injection of botulinum toxin type A. The results indicate that the botulinum toxin injection is a safe and useful therapy for synkinesis after peripheral facial palsy.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16390482

Analysis of human synovial sarcoma oncoprotein SYT-SSX and its therapeutic application.
Grants-in-Aid for Scientific Research
2004 - 2006
TANAKA Shinya, AKAGI Tsuyoshi, SAWA Hirofumi, MINAMI Akio
The cause of synovial sarcoma had been unknown for long time, and in 1994, Clark et al., identify the chimeric gene of t(X;18) and named it SYT-SSX. Then molecular analysis of SYT-SSX has been advanced and we have shown that SYT-SSX serves oncogenic potential on cells (Nagai, M., et al., PNAS, 2001).
In this project, SYT-SSX was found to bind to not only one of the chromatin remodeling factors, hBRM, but to BRG (Gene Cells, 9, 2004), and also shown to induce cellular senescence by the induction of p21 (Oncogene, 24, 2005). Furthermore, IGF2 has been shown to play an important role for growth of synovial sarcoma cells (Oncogene, 25, 2006). We have shown that signaling adaptor protein Crk is indispensable for tumorigenesity of synovial sarcoma cell lines (Mol. Cancer Res., 7, 2006).
One of the purpose of this project is to obtain the possible target molecules for synovial sarcoma treatment. As Crk knockdown cells is not going to die, but the malignant features were eliminated, thus, Crk may be the therapeutic target for the treatment of this sarcoma, and we will continue to analyze the mechanism of Crk for malignant character of synovial sarcoma.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 16390426

DNA damage checkpoint mechanism and its relation to aging
Grants-in-Aid for Scientific Research
2003 - 2004
MOTOYAMA Noboru, SAWA Hirofumi
Recent identification of human genes responsible for premature aging syndromes has revealed that the encoded proteins function in the cellular response to DNA damage and thereby contribute to the maintenance of genomic integrity. These findings thus suggest that defects in the DNA damage response can result in aging as well as in cancer. We investigated that the mechanisms of the activation and the function of the Chk2-p53 pathway and of the FOXO pathway in cells subjected to DNA damage as well as in the relations of these signaling pathways to aging and cancer. Here we have shown that Chk2 regulates p53 protein stabilization by phosphorylating Mdm2 on Ser78 and that Chk2 regulates both transcription-independent and transcription-dependent mechanisms of p53-mediated apoptosis by stabilizing p53 and by increasing its transcriptional regulatory activity. Moreover, we have found that ATM-Chk2-p53-dependent signaling pathway triggered by DNA damage is dispensable for the activation of stress-induced premature senescence to IR or oxidative stress. These results suggest that both ATM-Chk2-p53-dependent and -independent signaling pathway, apoptosis and senescence, act as a "security gate" to prevent neoplastic transformation. However, as a side effect, hyperactivity of the ATM-Chk2-p53 pathway caused apoptosis may also compromises organism homeostasis and eventually results in aging. FOXO family regulates various biological activities, including cell cycle progression, the cellular response to oxidative stress, DNA repair, and apoptosis, suggesting that FOXO also contributes genomic integrity. Furthermore, we have shown that mammalian SIRT1 interacts physically, functionally, and physiologically with FOXO, suggesting that FOXO family protein and SIRTl may cooperate to extend life span in response to restriction of caloric intake in mammals by preventing DNA damage accumulation.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 15370080

Molecular investigation on prognostic factors and development of an tailor-made therapy for Hunt syndrome.
Grants-in-Aid for Scientific Research
2002 - 2003
FURUTA Yasushi, SAWA Hirofumi, FUKUDA Satoshi
1.Varicella-zoster virus DNA level and facial paralysis in Ramsay Hunt syndrome
We have investigated whether the copy number of varicella-zoster virus (VZV) in saliva correlates with the clinical symptoms in patients with Ramsay Hunt syndrome (RHS). Patients with oropharyngeal zoster showed worse recovery of facial function than those without. It seems that the VZV DNA level in saliva reflects the kinetics of viral reactivation in the facial nerve as well as in the oropharyngeal epithelium in RHS patients.
2.Patterns of varicella-zoster virus reactivation in Ramsay Hunt syndrome
We analyzed the relationship between VZV load and onset of facial paralysis in 42 RHS patients. The results indicate that facial paralysis in RHS can occur at various times between the early and the regression phase of VZV reactivation, suggesting that there are variable patterns of development of facial nerve dysfunction caused by VZV reactivation and the progression of neuritis.
3.Serological diagnosis of varicella-zoster virus reactivation in patients with acute peripheral facial paralysis
We focused on the determination of an anti-VZV IgG antibody liter in sero-diagnosis by using an enzyme immunoassay (EIA) and investigated the diagnostic criteria for VZV reactivation by EIA. It was considered appropriate to give a diagnosis of VZV reactivation for those cases exhibiting a double-fold increasd in the VZV IgG EIA antibody titer.
4. Analysis of varicella-zoster virus load and cochleovestibular symptoms in patients with Ramsay Hunt syndrome
The present study analyzed the relationship between VZV load and the onset of the cochleovestibular symptoms. The results indicate that cochleovestibular symptoms can occur in various timing from the early phase to the regression phase of VZV reactivation, suggesting that there are various patterns in the development of the eighth cranial nerve dysfunction caused by VZV reactivation and progression of neuritis.
5.Varicella-zoster virus reactivation is the major cause of acute peripheral facial paralysis m children
This study analyzed the causes of acute peripheral facial paralysis in children by serological assays and PCR using paired sera and saliva samples. The results indicate that VZV reactivation is the major cause of acute peripheral facial paralysis in children, especially in ages between 6 and 15. In contrast, our data suggest that HSV-1 reactivation is not the major pathogenesis of Bell's palsy in children.
6.Analysis of patients with Bell's palsy who showed incomplete recovery
This study analyzed the causes of clinically diagnosed Bell's palsy who showed incomplete recovery of facial movement. The results indicate that VZV or HSV-1 reactivation is the major cause of Bell's palsy with poor prognosis.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), HOKKAIDO UNIVERSITY, 14571602

女性性殖器官に特異的な新規マトリックスメタロプロテアーゼMIFRの機能解析
科学研究費助成事業
1999 - 2003
大西 淳之, 澤 洋文, 大西 英理子, 松本 健一, 大西 英里子
組換え体ヒトMMP-23を作製し、293細胞で発現させたところ、MMP-23は2型の膜タンパクとして合成され、細胞内においてfurin様プロセシング酵素により切断されて分泌型へ変換された。この際、furinの膜結合領域を削除するとMMP-23のプロセシングが亢進しないことから、細胞内におけるMMP-23のプロセシングは膜上で行われる必要があることが示唆された。培養培地より組換え体MMP-23を精製し、その酵素としての特性を調べたところ、組換え体MMP-23は熱変性タイプIおよびIVコラーゲンを限定分解する活性を示したが、フィブロネクチン、ラミニン、ビトロネクチン、テネイシン、フィブリノーゲン、α1-アンチトリプシンに対して何ら切断活性を示さなかった。また組換え体MMP-23によるタイプIゼラチンの切断様式は他のMMP分子(MMP-2とMMP-14)とは異なる切断様式を示した。次にMMP-23の生理的な機能を検討するために、抗MMP-23中和抗体をラット卵巣の被膜下に注入したところ、正常血清を注入したラットや未処理のコントロールラットと比較して有意に排卵が阻害された。このことはMMP-23には他のMMP分子とは異なる基質特異性があり、排卵過程においてその酵素活性が関与していることを示している。
初代培養系ラット顆粒膜細胞を用いて、卵胞刺激ホルモン(FSH)によるMMP-23の転写抑制機序について解析を行った。FSHの作用により細胞内のサイクリックAMP産生が促進され、その結果、Aキナーゼとホスファチジルイノシトール3リン酸キナーゼ(PI3キナーゼ)の両者が活性化されることがMMP-23の転写抑制に必須であるが、更にPI3キナーゼの下流に位置するAktが関与することを新たに見出した。しかし、顆粒膜細胞内で単独にPI3キナーゼ/Aktの経路を活性化させてもMMP-23の転写抑制は起こらないことから、この転写調節には同時にAキナーゼからのシグナル伝達が活性化されている必要があることが判明した。
日本学術振興会, 特定領域研究, 北海道大学, 11240201

Analysis of transforming mechanism of human synovial sarcoma oncogene SYT-SSX
Grants-in-Aid for Scientific Research
2001 - 2002
TANAKA Shinya, AKAGI Tsuyoshi, MINAMI Akio, SAWA Hirofumi
Human synovial sarcoma occurs primarily around the joint of extremities and more than 90% of cases have chromosomal translocation t(X;18) resulting the formation of chimeric gene SYT-SSX (synovial sarcoma translocation-synovial sarcoma X break point). As both of SYT and SSX did not share any homology region of known functional proteins, the transforming mechanism of SYT-SSX has not yet been elucidated. In this project, we established rat fibroblast cell line 3Y1 expressing SYT, SSX, and SYT-SSX, and found that SYT-SSX induced anchorage-independent growth and tumor formation in nude mice. In this SYT-SSX expressing cell lines, one of the SWI/SNF type of chromatin remodeling factor hBRM has been shown to bind to SYT-SSX and this association was essential for the transformation of 3Y1 cells. Especially, as the disruption of the binding of SYT-SSX and hBRM by specific peptides composed of 50 amino acids corresponding to hBRM155-206, suppressed the growth of SYT-SSX-3Y1 cells, these peptides could be one of the basic technique for the establishment of gene therapy for synovial sarcoma. We also found that in contrast to 3Y1 cells, SYT-SSX induced growth suppression of human adenocarcinoma cell line SW13. In this cell line, SYT-SSX induced p21WAF1/CIP1 expression confirmed by immunoblotting. The luciferase assay using p21 promoter-regulated construction, SYT-SSX was found to activate p21 promoter by transcription factor Sp1-dependent and p53-independent mechanism. Thus, SYT-SSX has differential effect for cell growth such as growth positive and growth negative mechanism, in different cell lines. We are currently considering the augmentation of growth negative function of SYT-SSX may induce the tumor cell suppression as a specific therapy of synovial sarcoma.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), HOKKAIDO UNIVERSITY, 13557122