Lanka virus, a Mus booduga-borne orthohantavirus infection-associated febrile illness in Sri Lanka
Devinda S. Muthusinghe, Pavani Senarathne, Kenta Shimizu, Yomani D. Sarathkumara, Shanika Nanayakkara, Sithumini M.W. Lokupathirage, Zhouoxing Wei, Nipun S. Rathnayake, Rydhnieya Vijeyakumaran, Nobuo Koizumi, Tomonori Kawakami, Akio Koizumi, Kouji H. Harada, Nilanthi Dissanayake, Senanayake A. M. Kularathne, Yoshimi Tsuda, Shuzo Urata, Jiro Arikawa, Chandika D. Gamage, Kumiko Yoshimatsu
PLOS Neglected Tropical Diseases, 19, 6, e0013169, e0013169, Public Library of Science (PLoS), 11 Jun. 2025, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal, Background

In Sri Lanka, a high seroprevalence of antibodies against hantaviruses was reported in communities affected by chronic kidney disease of unknown etiology (CKDu). Recently, two rodent-borne hantaviruses, Lanka virus and Anjozorobe virus, were identified in these areas. However, it is unclear which virus is the source of infection in humans, and its pathogenicity is unknown.

Methodology/principal findings

A total of 181 sera from febrile patients from two CKDu-endemic regions, Girandurukotte and Polonnaruwa, were examined and Lanka virus genome was detected in two IgM-positive febrile patients. Of 76 serum samples from patients with fever of unknown etiology collected during 2016 examined to identify hantavirus genomes, antibodies, and serotypes, 10 were IgG-positive with five of them having IgM also. They were all without clinical features of hemorrhagic fever with renal syndrome, but three patients required treatment in the intensive care unit. A serotyping strategy was established based on the antigenic difference of the glycoprotein Gn of Lanka and Anjozorobe viruses. Using this method, febrile patients were found to be infected with the Lanka virus and none of the patient sera showed Anjozorobe virus infection pattern. Additionally, a total of 373 previously diagnosed seropositive serum samples from CKDu patients and healthy residents were serotyped to categorize 87% of seropositives as Lanka virus infection.

Conclusions/significance

Lanka virus carried by little Indian field mouse (Mus booduga) is transmitted to humans, likely causing febrile illness occasionally while leading to severe disease in some of the febrile patients.

Urinalysis of a Hantaan virus-infected mouse model of hemorrhagic fever with renal syndrome.
Rakiiya S Sarii, Pavani Senarathne, Kumiko Yoshimatsu
The Journal of veterinary medical science, 14 May 2025, [Peer-reviewed], [Corresponding author], [Domestic magazines]
English, Scientific journal, Hantaan virus causes hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease. Korean hemorrhagic fever virus (KHFV), a strain of Hantaan virus, showed symptoms in mice similar to those of HFRS patients, including weight loss, renal medullary hemorrhage, hepatitis, and neutrophilia. Therefore, mice inoculated with KHFV were expected to serve as a model for HFRS. However, urinary symptoms characteristic of HFRS, such as proteinuria and hematuria, have not yet been examined. In this study, we attempted to evaluate renal function by analyzing urine. As a result, in mice inoculated with KHFV, oliguria and hematuria accompanied by weight loss were observed at 5-8 days after inoculation, and albuminuria was also observed. In addition, the viral load in the kidney and viral excretion into the urine were observed. When the neutralizing monoclonal antibody HCO2 against Hantaan virus was administered before inoculation, all symptoms were abolished. To clarify the therapeutic effect of HCO2 antibody, it was administered intravenously on days 1, 3, and 5 after infection. Weight loss and renal medullary hemorrhage were suppressed, and histological examination revealed micro renal hemorrhage in mice on day 5 administration. It was found that neutralizing antibody can be expected to alleviate symptoms even if it is administered late, and that early administration is more effective. These results indicate that this mouse model shows symptoms like human HFRS and can be used to evaluate antiviral effects.

Serological detection of antibodies against batborne and shrew-borne hantaviruses in Sri Lanka
Rakiiya Sikatarii Sarii, Pavani Senarathne, Chandika D Gamage, Kumiko Yoshimatsu
Japanese Journal of Veterinary Research, 73, 2, 52, 59, May 2025, [Peer-reviewed], [Last author, Corresponding author]
English, Research institution

Orthohantavirus seoulense as a cause of acute, dengue-negative febrile illness in southern Vietnam.
Mai Thi Quynh Le, Kumiko Yoshimatsu, Haruka Abe, Thuy Thi Nguyen, Hang Le Khanh Nguyen, Trang Thi Hong Ung, Phuong Vu Mai Hoang, Nobuo Koizumi, Futoshi Hasebe, Kozue Miura
Transactions of the Royal Society of Tropical Medicine and Hygiene, 12 Apr. 2025, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Dengue fever has surged in Vietnam since 2021; however, the aetiology of non-dengue undifferentiated febrile illnesses remains poorly understood. METHODS: Fifty whole blood samples that tested negative in rapid tests for anti-dengue virus antibodies (IgM and IgG) and NS1 viral antigen at Vung Tau General Hospital, southern Vietnam, were subjected to nucleic acid amplification tests for flaviviruses, hantaviruses, Leptospira spp. and Orientia tsutsugamushi, followed by DNA sequencing. The plasma samples were also tested for anti-hantavirus IgM and IgG antibodies using ELISA. RESULTS: Of the 50 samples, eight were PCR-positive for flaviviruses and two were positive for hantaviruses. Sequencing analysis revealed that three and five of the eight flavivirus-positive samples were dengue virus type 1 and dengue virus type 2, respectively. The hantavirus species was identified as Orthohantavirus seoulense (SEOV). None of the patients tested positive for Leptospira spp. or O. tsutsugamushi. Anti-hantavirus IgM and IgG antibodies were detected in five and four patients, respectively. CONCLUSIONS: This study suggests that SEOV is a notable contributor to dengue-negative febrile illnesses in southern Vietnam. ACCESSION NUMBER: LC822654.

Characterization of quasispecies of severe fever with thrombocytopenia syndrome virus
Sithumini M. W. Lokupathirage, Devinda S. Muthusinghe, Rakiiya S. Sarii, Olusola A. Akanbi, Kenta Shimizu, Yoshimi Tsuda, Kumiko Yoshimatsu
Journal of Virology, e0179424, 09 Apr. 2025, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Three specific amino acid variations have been identified in the quasispecies of the isolated YG1 strain of severe fever with thrombocytopenia syndrome virus (SFTSV): Gn (Y328H), Gc (R624W), and L (N1891K). The Gn (Y328H) accounted for 26.9% of the viruses in the patient's blood. The other two mutations are less frequent, indicating that these mutations appeared during propagation in Vero E6 cells. To investigate the effects of each mutation on viral properties, we evaluated viruses with one to three mutations. Mutations Y328H and R624W in glycoprotein (GP) resulted in increased plaque size and cell fusion activity. Viruses with the N1891K mutation in L showed a notable cytopathic effect (CPE), which was inhibited by a pan-caspase inhibitor, suggesting that caspase-dependent cell death occurred. Programmed cell death-associated caspases were induced in both CPE-inducing and wild-type virus-infected cells. Furthermore, infection with the wild-type virus suppressed actinomycin D-induced cell death. These results suggest that SFTSV-infected cells initiate programmed cell death, whereas the wild-type virus inhibits cell death. Additionally, the recombinant single mutant virus outcompeted by a 10-fold lower amount of the wild-type virus in Vero E6 cells, indicating that the mutations were not advantageous for viral propagation in Vero E6 cells. These findings suggest that the quasispecies composition of SFTSV is influenced by the propagative environment.IMPORTANCEThis study presents findings on viral pathogenesis by analyzing quasispecies derived from a fatal case of severe fever with thrombocytopenia syndrome virus (SFTSV) infection. Analysis of recombinant SFTSV with mutations in Gn and Gc suggested that combinations of mutations may enhance the viability of mutant viruses, thereby selecting viruses to create a suitable population for propagation. The N1891K mutation in the L protein of SFTSV is associated with promoting cytopathic effects (CPE). Conversely, the wild-type virus, which is the predominant virus in infected patients, suppresses cell death. It has been suggested that SFTSV possesses a mechanism to evade cell death for prolonged viral propagation within the infected cells. Although the precise mechanism remains unknown, RNA virus polymerase may be involved in regulating cell death. This study contributes to our understanding of the mechanisms underlying the adaptation and survival of viruses as quasispecies.

Evolution of BA.2.86 to JN.1 reveals functional changes in non-structural viral proteins are required for fitness of SARS-CoV-2
Shuhei Tsujino, Masumi Tsuda, Naganori Nao, Kaho Okumura, Lei Wang, Yoshitaka Oda, Yume Mimura, Jingshu Li, Rina Hashimoto, Yasufumi Matsumura, Rigel Suzuki, Saori Suzuki, Kumiko Yoshimatsu, Miki Nagao, Jumpei Ito, Kazuo Takayama, Kei Sato, Keita Matsuno, Tomokazu Tamura, Shinya Tanaka, Takasuke Fukuhara
Cold Spring Harbor Laboratory, 19 Feb. 2025, [Peer-reviewed]
ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), is still circulating among humans, leading to the continuous evolution. SARS-CoV-2 Omicron JN.1 evolved from a distinct SARS-CoV-2 lineage, BA.2.86, spread rapidly worldwide. It is unclear why BA.2.86 did not become dominant and was quickly replaced by JN.1, which possesses one amino acid substitution in the spike protein (S:L455S) and two in the non-spike proteins NSP6 and ORF7b (NSP6:R252K and ORF7b:F19L) compared to BA.2.86. Here, we utilized recombinant viruses to elucidate the impact of these mutations on the virological characteristics of JN.1. We found that the mutation in the spike attenuated viral replication, but the non-spike mutations enhanced replication, suggesting the mutations in the non-spike proteins compensate for the one in the spike to improve viral fitness, as the mutations in the spike contribute to further immune evasion. Our findings suggest that functional changes in both the spike and non-spike proteins are necessary in the evolution of SARS-CoV-2 to enable evasion of adaptive immunity within the human population while sustaining replication.

IMPORTANCE

Because the spike protein is strongly associated with certain virological properties of SARS-CoV-2, such as immune evasion and infectivity, most previous studies on SARS-CoV-2 variants have focused on spike protein mutations. However, the non-spike proteins also contribute to infectivity, as observed throughout the evolution of Omicron subvariants. In this study, we demonstrate a “trade-off” strategy in SARS-CoV-2 Omicron JN.1 in which the reduced infectivity caused by spike mutation is compensated by non-spike mutations. Our results provide insight into the evolutionary scenario of the emerging virus in the human population.

Two amino acid pairs in the Gc glycoprotein of severe fever with thrombocytopenia syndrome virus responsible for the enhanced virulence.
Shelly Wulandari, Samuel Nyampong, Michaela Beránková, Sithumini M W Lokupathirage, Kumiko Yoshimatsu, Hiroshi Shimoda, Daisuke Hayasaka
Virology, 601, 110294, 110294, Jan. 2025, [Peer-reviewed], [International Magazine]
English, Scientific journal, Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no fatality. We identified a pair of amino acid residues in the Gc protein, glycine and serine, at residues 581 and 934, respectively, derived from Tk-F123, leading to a fatal infection. Those in Ng-F264 were arginine and asparagine. These results suggest that this pair of residues affects the Gc protein function and regulates SFTSV virulence. Our findings provide useful clues for the elucidation of viral pathogenicity and the development of effective live-attenuated vaccines and antiviral strategies.

Development of a seroepidemiological tool for bat-borne and shrew-borne hantaviruses and its application using samples from Zambia
Rakiiya Sikatarii Sarii, Masahiro Kajihara, Zuoxing Wei, Sithumini M. W. Lokpathirage, Devinda S. Muthusinghe, Akina Mori-Kajihara, Katendi Changula, Yongjin Qiu, Joseph Ndebe, Bernard M. Hang’ombe, Fuka Kikuchi, Ai Hayashi, Motoi Suzuki, Hajime Kamiya, Satoru Arai, Ayato Takada, Kumiko Yoshimatsu
PLOS Neglected Tropical Diseases, 18, 11, e0012669, e0012669, Public Library of Science (PLoS), 21 Nov. 2024, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Background

Rodent-borne orthohantaviruses are the causative agents of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Apart from the classic rodent-borne hantaviruses, numerous species of hantaviruses have been identified in shrews and bats; however, their antigenicity and pathogenicity are unknown. This study focused on developing a serological method to detect antibodies against bat- and shrew-borne hantaviruses.

Methodology/Principal findings

Five bat-borne (Brno, Dakrong, Quezon, Robina, and Xuan Song) and 6 shrew-borne (Asama, Altai, Cao Bang, Nova, Seewis, and Thottapalayam) viruses were selected based on the phylogenetic differences in their N proteins. The recombinant N (rN) proteins of these viruses were expressed as antigens in Vero E6 and 293T cell lines using the pCAGGS/MCS vector. Antisera against the Nus-tagged rN fusion proteins of these viruses (mouse anti-Brno, Dakrong, Quezon, Robina, Xuan Song, Asama, Cao Bang, and Nova, while rabbit anti-Altai, Seewis and Thottapalayam) were also generated. Antigenic cross-reactivity was examined in antisera and rN-expressing Vero E6 cells. The rN proteins of almost all the tested viruses, except for the Quezon and Robina viruses, showed independent antigenicity. For serological screening of bat samples, 5 rNs of the bat-borne viruses were expressed together in a single transfection protocol. Similarly, 6 rNs of shrew-borne viruses were expressed. Reactivities of the mixed antigen system were also examined across the singly transfected Vero cell lines to ensure that all antigens were expressed. Using these antigens, bat serum samples collected from Zambia were screened using the indirect immunofluorescence antibody test (IFAT). Selected positive samples were individually tested for the respective antigens by IFAT and western blot assays using rN-expressing 293T cell lysates. Of the 1,764 bat serum samples tested, 11.4% and 17.4% were positive for bat and shrew mixed antigens, respectively. These samples showed positive reactions to the Brno, Dakrong, Quezon, Xuan Son, Robina, Asama, Altai, Cao Bang, or Thottapalayam virus antigens.

Conclusions/Significance

These observations suggest that the mixed-antigen screening system is useful for serological screening For Orthohantavirus infections and that bats in Zambia are likely exposed to not only bat-borne hantaviruses but also to shrew-borne hantaviruses.

Coinfection with Orthohantavirus and Leptospira spp. in Rats Collected from Markets in Indonesia.
Kozue Miura, James Chambers, Naohiro Takahashi, Harimurti Nuradji, Nlp Indi Dharmayanti, Susanti, Parriantariksina Randusari, Susan M Noor, Rahmat Setya Adji, Muharam Saepulloh, Sumarningsih, Kumiko Yoshimatsu, Nobuo Koizumi
Vector borne and zoonotic diseases (Larchmont, N.Y.), 25, 1, 43, 48, 18 Oct. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background: Rats are an important reservoir animal for several zoonotic pathogens worldwide, including hantaviruses and Leptospira spp., which are the causative agents of hemorrhagic fever with renal syndrome, hantavirus cardiopulmonary syndrome, and leptospirosis. Although a previous study indicated a high frequency of antihantaviral antibodies in patients with acute fever in Indonesia, circulating hantaviruses and their reservoir animals in the country remain limited. Materials and Methods: The presence of hantavirus in rats captured in the urban area of Bogor, Indonesia, from which Leptospira spp. were isolated using PCR, followed by DNA sequencing. Immunohistochemical analyses were performed to detect hantaviral and leptospiral antigens in rat kidney tissues. Results: Seoul of Orthohantavirus seoulense (SEOV) RNA was detected from 24 of 80 Rattus norvegicus (30%). SEOV and Leptospira coinfection was detected in 10 of 80 rats (12.5%). Immunohistochemistry revealed that hantavirus antigens were positively stained in the interstitial capillaries and cells, whereas Leptospira antigens were stained in the luminal side of the renal tubules. Conclusion: This study revealed a high prevalence of SEOV and SEOV and Leptospira coinfection among rats in the urban areas of Bogor, Indonesia, indicating a potential risk of rat-borne zoonotic diseases in the area.

Development of an entirely cloned cDNA-based reverse genetics system for Tofla virus of orthonairovirus
Shelly Wulandari, Samuel Nyampong, Sithumini M.W. Lokupathirage, Kumiko Yoshimatsu, Hiroshi Shimoda, Daisuke Hayasaka
Virology, 598, 110170, 110170, Elsevier BV, Oct. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, The genus Orthonairovirus includes highly pathogenic tick-borne viruses such as the Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV). A reverse genetics system is an indispensable tool for determining the viral factors related to pathogenicity. Tofla orthonairovirus (TFLV) is a recently identified virus isolated from ticks in Japan and our research has suggested that TFLV is a useful model for studying pathogenic orthonairoviruses. In this study, we successfully established a reverse genetics system for TFLV using T7 RNA polymerase. Recombinant TFLV was generated by transfecting cloned complementary DNAs encoding the TFLV genome into BSR T7/5 cells expressing T7 RNA polymerase. We were able to rescue infectious recombinant TFLV mutant (rTFLVmt) and wild-type TFLV (rTFLVpt) viruses, which exhibited indistinguishable growth kinetics in mammalian cells and pathogenicity in A129 mice compared with the authentic virus. Our approach provides a valuable method for establishing reverse genetics system for orthonairoviruses.

Involvement of SARS-CoV-2 accessory proteins in immunopathogenesis.
Hayato Ito, Tomokazu Tamura, Lei Wang, Kento Mori, Masumi Tsuda, Rigel Suzuki, Saori Suzuki, Kumiko Yoshimatsu, Shinya Tanaka, Takasuke Fukuhara
Microbiology and immunology, 68, 7, 237, 247, Jul. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the largest single-stranded RNA virus known to date. Its genome contains multiple accessory protein genes that act against host immune responses but are not required for progeny virus production. The functions of the accessory proteins in the viral life cycle have been examined, but their involvement in viral pathogenicity remains unclear. Here, we investigated the roles of the accessory proteins in viral immunopathogenicity. To this end, recombinant SARS-CoV-2 possessing nonsense mutations in the seven accessory protein open reading frames (ORFs) (ORF3a, ORF3b, ORF6, ORF7a, ORF8, ORF9b, and ORF10) was de novo generated using an early pandemic SARS-CoV-2 strain as a backbone. We confirmed that the resultant virus (termed ORF3-10 KO) did not express accessory proteins in infected cells and retained the desired mutations in the viral genome. In cell culture, the ORF3-10 KO virus exhibited similar virus growth kinetics as the parental virus. In hamsters, ORF3-10 KO virus infection resulted in mild weight loss and reduced viral replication in the oral cavity and lung tissue. ORF3-10 KO virus infection led to mild inflammation, indicating that an inability to evade innate immune sensing because of a lack of accessory proteins impairs virus growth in vivo and results in quick elimination from the body. Overall, we showed that SARS-CoV-2 accessory proteins are involved in immunopathogenicity.

Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant
Tomokazu Tamura, Takashi Irie, Sayaka Deguchi, Hisano Yajima, Masumi Tsuda, Hesham Nasser, Keita Mizuma, Arnon Plianchaisuk, Saori Suzuki, Keiya Uriu, Mst Monira Begum, Ryo Shimizu, Michael Jonathan, Rigel Suzuki, Takashi Kondo, Hayato Ito, Akifumi Kamiyama, Kumiko Yoshimatsu, Maya Shofa, Rina Hashimoto, Yuki Anraku, Kanako Terakado Kimura, Shunsuke Kita, Jiei Sasaki, Kaori Sasaki-Tabata, Katsumi Maenaka, Naganori Nao, Lei Wang, Yoshitaka Oda, Hirofumi Sawa, Ryoko Kawabata, Yukio Watanabe, Ayaka Sakamoto, Naoko Yasuhara, Tateki Suzuki, Yukari Nakajima, Zannatul Ferdous, Kenji Shishido, Yuka Mugita, Otowa Takahashi, Kimiko Ichihara, Yu Kaku, Naoko Misawa, Ziyi Guo, Alfredo Hinay, Yusuke Kosugi, Shigeru Fujita, Jarel M. Tolentino, Luo Chen, Lin Pan, Mai Suganami, Mika Chiba, Ryo Yoshimura, Kyoko Yasuda, Keiko Iida, Naomi Ohsumi, Adam P. Strange, Yuki Shibatani, Tomoko Nishiuchi, Shiho Tanaka, Olivia Putri, Gustav Joas, Yoonjin Kim, Daichi Yamasoba, Kazuhisa Yoshimura, Kenji Sadamasu, Mami Nagashima, Hiroyuki Asakura, Isao Yoshida, So Nakagawa, Akifumi Takaori-Kondo, Kotaro Shirakawa, Kayoko Nagata, Ryosuke Nomura, Yoshihito Horisawa, Yusuke Tashiro, Yugo Kawai, Takamasa Ueno, Chihiro Motozono, Mako Toyoda, Terumasa Ikeda, Akatsuki Saito, Keita Matsuno, Jumpei Ito, Shinya Tanaka, Kei Sato, Takao Hashiguchi, Kazuo Takayama, Takasuke Fukuhara
Nature Communications, 15, 1, 305, 330, Springer Science and Business Media LLC, 08 Feb. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, Abstract

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.

Akaluc bioluminescence offers superior sensitivity to trackin vivodynamics of SARS-CoV-2 infection
Tomokazu Tamura, Hayato Ito, Shiho Torii, Lei Wang, Rigel Suzuki, Shuhei Tusjino, Akifumi Kamiyama, Yoshitaka Oda, Yuhei Morioka, Saori Suzuki, Kotaro Shirakawa, Kei Sato, Kumiko Yoshimatsu, Yoshiharu Matsuura, Satoshi Iwano, Shinya Tanaka, Takasuke Fukuhara
iScience, 27, 5, 109647, 109647, Cold Spring Harbor Laboratory, 13 Oct. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Summary

Monitoringin vivoviral dynamics can improve our understanding of pathogenicity and tissue tropism. For positive-sense, single-stranded RNA viruses, several studies have attempted to monitor viral kineticsin vivousing reporter genomes. The application of such recombinant viruses can be limited by challenges in accommodating bioluminescent reporter genes in the viral genome. Conventional luminescence also exhibits relatively low tissue permeability and thus less sensitivity for visualizationin vivo. Here we show that unlike NanoLuc bioluminescence, the improved method, termed AkaBLI, allows visualization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Syrian hamsters. By successfully incorporating a codon-optimized Akaluc luciferase gene into the SARS-CoV-2 genome, we visualizedin vivoinfection, including the tissue-specific differences associated with particular variants. Additionally, we could evaluate the efficacy of neutralizing antibodies and mRNA vaccination by monitoring changes in Akaluc signals. Overall, AkaBLI is an effective technology for monitoring viral dynamics in live animals.

Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics.
Izumi Kimura, Daichi Yamasoba, Hesham Nasser, Hayato Ito, Jiri Zahradnik, Jiaqi Wu, Shigeru Fujita, Keiya Uriu, Jiei Sasaki, Tomokazu Tamura, Rigel Suzuki, Sayaka Deguchi, Arnon Plianchaisuk, Kumiko Yoshimatsu, Yasuhiro Kazuma, Shuya Mitoma, Gideon Schreiber, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Akifumi Takaori-Kondo, Jumpei Ito, Kotaro Shirakawa, Kazuo Takayama, Takashi Irie, Takao Hashiguchi, So Nakagawa, Takasuke Fukuhara, Akatsuki Saito, Terumasa Ikeda, Kei Sato
Journal of virology, 97, 10, e0101123, 05 Oct. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Previous studies on the Omicron BA.2 variant suggested that the virological characteristics of BA.2 are determined by the mutations in at least two different regions of the viral genome: in the BA.2 spike gene (enhancing viral fusogenicity and intrinsic pathogenicity) and the non-spike region of the BA.2 genome (leading to intrinsic pathogenicity attenuation). However, the mutations modulating the BA.2 virological properties remain elusive. In this study, we demonstrated that the L371F substitution in the BA.2 spike protein confers greater fusogenicity and intrinsic pathogenicity. Furthermore, we revealed that multiple mutations downstream of the spike gene in the BA.2 genome are responsible for attenuating intrinsic viral pathogenicity and replication capacity. As mutations in the SARS-CoV-2 variant spike proteins could modulate certain virological properties, such as immune evasion and infectivity, most studies have previously focused on spike protein mutations. Our results underpin the importance of non-spike protein-related mutations in SARS-CoV-2 variants. IMPORTANCE Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.

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, Isao Yokota, Keita Matsuno, Kazuo Takayama, Shinya Tanaka, Kei Sato, Takasuke Fukuhara
Communications biology, 6, 1, 772, 772, 24 Jul. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Insufficient serological evidence of the association between chronic kidney disease and leptospirosis in Badulla and Kandy districts, Sri Lanka
Regina Amanda Fonseka, Pavani Senarathne, Devinda Shameera Muthusinghe, Nishantha Nanayakkara, Lishantha Gunaratne, Kumiko Yoshimatsu, Nobuo Koizumi, Chandika Damesh Gamage
01 Jun. 2023

Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.
Tomokazu Tamura, Jumpei Ito, Keiya Uriu, Jiri Zahradnik, Izumi Kida, Yuki Anraku, Hesham Nasser, Maya Shofa, Yoshitaka Oda, Spyros Lytras, Naganori Nao, Yukari Itakura, Sayaka Deguchi, Rigel Suzuki, Lei Wang, Mst Monira Begum, Shunsuke Kita, Hisano Yajima, Jiei Sasaki, Kaori Sasaki-Tabata, Ryo Shimizu, Masumi Tsuda, Yusuke Kosugi, Shigeru Fujita, Lin Pan, Daniel Sauter, Kumiko Yoshimatsu, Saori Suzuki, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Yuki Yamamoto, Tetsuharu Nagamoto, Gideon Schreiber, Katsumi Maenaka, Takao Hashiguchi, Terumasa Ikeda, Takasuke Fukuhara, Akatsuki Saito, Shinya Tanaka, Keita Matsuno, Kazuo Takayama, Kei Sato
Nature communications, 14, 1, 2800, 2800, 16 May 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.

Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant.
Jumpei Ito, Rigel Suzuki, Keiya Uriu, Yukari Itakura, Jiri Zahradnik, Kanako Terakado Kimura, Sayaka Deguchi, Lei Wang, Spyros Lytras, Tomokazu Tamura, Izumi Kida, Hesham Nasser, Maya Shofa, Mst Monira Begum, Masumi Tsuda, Yoshitaka Oda, Tateki Suzuki, Jiei Sasaki, Kaori Sasaki-Tabata, Shigeru Fujita, Kumiko Yoshimatsu, Hayato Ito, Naganori Nao, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Yuki Yamamoto, Tetsuharu Nagamoto, Jin Kuramochi, Gideon Schreiber, Akatsuki Saito, Keita Matsuno, Kazuo Takayama, Takao Hashiguchi, Shinya Tanaka, Takasuke Fukuhara, Terumasa Ikeda, Kei Sato
Nature communications, 14, 1, 2671, 2671, 11 May 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

Effects of Diazinon Exposure on Urinary Shedding of Leptospira interrogans Serogroup Hebdomadis in Mice
So Shinya, Devinda S. Muthusinghe, Nobuo Koizumi, Kumiko Yoshimatsu, Shouta M. M. Nakayama, Mayumi Ishizuka, Yoshinori Ikenaka
Toxics, 11, 4, 11 Apr. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Wild rodents are natural hosts of Leptospira spp. and are exposed to various pesticides, some of which are immunotoxic. Rodent urine is an important source of infection for humans and other animals. We evaluated the effects of pesticide exposure on Leptospira growth in mice. Diazinon, at doses of 0.2, 1, and 5 mg/kg/day, was orally administered continuously to mice infected with Leptospira interrogans serogroup Hebdomadis for 32 days. The numbers of L. interrogans in urine and kidney tissues were significantly lower in mice exposed to 5 mg/kg/day diazinon than in unexposed mice (p < 0.05). The urinary concentration of 2-isopropyl-6-methyl-4-pyrimidinol, the metabolite of diazinon, was comparable with the concentration at which viability of L. interrogans was decreased in in vitro assay, suggesting that it had toxic effects on L. interrogans in the proximal renal tubules. Diazinon exposure reinforced Leptospira-induced expression of inflammatory cytokine genes in kidney tissues, and an enhanced immune system might suppress Leptospira growth. These results suggest that diazinon exposure may not increase the risk of Leptospira transmission to humans through mice. This novel study evaluated the relationship between pesticide exposure and Leptospira infection in mice, and the results could be useful for risk assessment of leptospirosis.

Hantavirus infection as a risk factor for chronic kidney disease of unknown aetiology (CKDu) and its prevalence in endemic areas of Sri Lanka since 2010 according to a retrospective serological analysis
Chandika Damesh Gamage, Shanika Nanayakkara, Yomani D. Sarathkumara, Devinda S. Muthusinghe, Kenta Shimizu, Jiro Arikawa, Sithumini M. W. Lokupathirage, Nishantha Nanayakkara, Lishanthe Gunarathne, Rohana Chandrajith, Kouji H. Harada, Akio Koizumi, Kumiko Yoshimatsu
Journal of Medical Microbiology, 71, 12, Microbiology Society, 16 Dec. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal,
Background. Chronic kidney disease of unknown aetiology (CKDu) is a major public health problem in Sri Lanka, especially among agrarian communities. Although the cause of CKDu is still unknown, hantavirus infection has been proposed as a risk factor.

Methods. This study was performed using serological samples collected from two CKDu-endemic areas, Anuradhapura (2010) and Badulla districts (2010 and 2016), and a non-endemic area, Matale (2016) district. The presence of anti-Thailand orthohantavirus IgG antibodies was investigated in serum samples. Hantavirus seroprevalence and demographic data were epidemiologically analysed.

Results. Seroprevalence was higher in CKDu patients (40.6–60.0 %) and healthy individuals in CKDu-endemic areas (17.6–25.5 %) than in healthy individuals in non-endemic areas (3.0 %). Statistically significant odds ratios (ORs) for hantavirus infection in CKDu patients were detected in CKDu-endemic areas [ORs: 3.2 and 3.1; 95 % confidence interval (CI): 1.8–5.5 and 1.8–5.2 in Anuradhapura and Badulla districts in 2010; and OR: 4.4, 95 % CI: 2.3–8.5 in 2016 in Badulla district). Furthermore, the OR for hantavirus infection in Badulla district has increased in the last decade from 3.1 (95 % CI: 1.8–5.3) to 4.4 (95 % CI: 2.3–8.5).

Conclusion. Hantavirus infection has been prevalent in two distant CKDu-endemic areas since 2010. The observed significant association of hantavirus seropositivity with CKDu indicates a possible role of hantavirus infection in CKDu pathogenesis., 31839138

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, [Peer-reviewed], [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.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5.
Izumi Kimura, Daichi Yamasoba, Tomokazu Tamura, Naganori Nao, Tateki Suzuki, Yoshitaka Oda, Shuya Mitoma, Jumpei Ito, Hesham Nasser, Jiri Zahradnik, Keiya Uriu, Shigeru Fujita, Yusuke Kosugi, Lei Wang, Masumi Tsuda, Mai Kishimoto, Hayato Ito, Rigel Suzuki, Ryo Shimizu, Mst Monira Begum, Kumiko Yoshimatsu, Kanako Terakado Kimura, Jiei Sasaki, Kaori Sasaki-Tabata, Yuki Yamamoto, Tetsuharu Nagamoto, Jun Kanamune, Kouji Kobiyama, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, Kotaro Shirakawa, Akifumi Takaori-Kondo, Jin Kuramochi, Gideon Schreiber, Ken J Ishii, Takao Hashiguchi, Terumasa Ikeda, Akatsuki Saito, Takasuke Fukuhara, Shinya Tanaka, Keita Matsuno, Kei Sato
Cell, 185, 21, 3992, 4007, 13 Oct. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

Pathological Studies on Hantaan Virus-Infected Mice Simulating Severe Hemorrhagic Fever with Renal Syndrome
Zhouoxing Wei, Kenta Shimizu, Rakiiya S. Sarii, Devinda S. Muthusinghe, Sithumini M. W. Lokupathirage, Junko Nio-Kobayashi, Kumiko Yoshimatsu
Viruses, 14, 10, 2247, 2247, MDPI AG, 13 Oct. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Hantaan virus is the causative agent of hemorrhagic fever with renal syndrome (HFRS). The Hantaan virus strain, Korean hemorrhagic fever virus clone-5 (KHF5), causes weight loss and renal hemorrhage in laboratory mice. Clone-4 (KHF4), which has a single E417K amino acid change in its glycoprotein, is an avirulent variant. In this study, KHF4 and KHF5 were compared to evaluate pathological differences in mice in vitro and in vivo. The characteristics of the two glycoproteins were not significantly different in vitro. However, the virulent KHF5 strain targeted the lungs and caused pneumonia and edema in vivo. Both strains induced high infectivity levels in the liver and caused hepatitis; however, petechial hemorrhage and glycogen storage reduction were observed in KHF5-infected mice alone. Renal hemorrhage was observed using viral antigens in the tubular region of KHF5-infected mice. In addition, an increase in white blood cell levels and neutrophilia were found in KHF5-infected mice. Microarray analysis of liver cells showed that CD8+ T cell activation, acute-phase protein production, and neutrophil activation was induced by KHF5 infection. KHF5 infectivity was significantly increased in vivo and the histological and clinicopathological findings were similar to those in patients with HFRS.

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, Proceedings of the National Academy of Sciences, 06 Sep. 2022, [Peer-reviewed], [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.

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, [Peer-reviewed], [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.

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.

Subcellular localization of nucleocapsid protein of SFTSV and its assembly into the ribonucleoprotein complex with L protein and viral RNA.
Sithumini M W Lokupathirage, Yoshimi Tsuda, Kodai Ikegame, Kisho Noda, Devinda S Muthusinghe, Fumiya Kozawa, Rashid Manzoor, Kenta Shimizu, Kumiko Yoshimatsu
Scientific reports, 11, 1, 22977, 22977, 26 Nov. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes novel zoonotic diseases in Asian countries including China, Japan, South Korea, and Vietnam. In phleboviruses, viral proteins play a critical role in viral particle formation inside the host cells. Viral glycoproteins (GPs) and RNA-dependent RNA polymerase (RdRp) are colocalized in the Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The nucleocapsid (N) protein was widely expressed in the cytoplasm, even in cells coexpressing GP. However, the role of SFTSV N protein remains unclear. The subcellular localization of SFTSV structural proteins was investigated using a confocal microscope. Subsequently, minigenome and immunoprecipitation assays were carried out. The N protein interacts with viral RNA (vRNA) and further shows translational activity with RdRp which is L protein and localized in the ERGIC and Golgi apparatus when co-expressed with GP. On the other hand, mutant N protein did not interact with vRNA either localized in the ERGIC or Golgi apparatus. The interaction between the N protein of SFTSV and vRNA is important for the localization of viral proteins and viral assembly. This study provides useful insights into the life cycle of SFTSV, which will lead to the detection of antiviral targets.

Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation.
Akatsuki Saito, Takashi Irie, Rigel Suzuki, Tadashi Maemura, Hesham Nasser, Keiya Uriu, Yusuke Kosugi, Kotaro Shirakawa, Kenji Sadamasu, Izumi Kimura, Jumpei Ito, Jiaqi Wu, Kiyoko Iwatsuki-Horimoto, Mutsumi Ito, Seiya Yamayoshi, Samantha Loeber, Masumi Tsuda, Lei Wang, Seiya Ozono, Erika P Butlertanaka, Yuri L Tanaka, Ryo Shimizu, Kenta Shimizu, Kumiko Yoshimatsu, Ryoko Kawabata, Takemasa Sakaguchi, Kenzo Tokunaga, Isao Yoshida, Hiroyuki Asakura, Mami Nagashima, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa, Kazuhisa Yoshimura, Akifumi Takaori-Kondo, Masaki Imai, Shinya Tanaka, So Nakagawa, Terumasa Ikeda, Takasuke Fukuhara, Yoshihiro Kawaoka, Kei Sato
Nature, 602, 7896, 300, 306, 25 Nov. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

Identification of Novel Rodent-Borne Orthohantaviruses in an Endemic Area of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka
Devinda S. Muthusinghe, Kenta Shimizu, Sithumini M, W. Lokupathirage, Zhouoxing Wei, Yomani D. Sarathkumara, G. R. Am, a Fonseka, Pavani Senarathne, Nobuo Koizumi, Tomonori Kawakami, Akio Koizumi, Chaminda Wickramasinghe, Hideki Ebihara, Keita Matsuno, Yoshimi Tsuda, Jiro Arikawa, Chandika D. Gamage, Kumiko Yoshimatsu
Viruses, 13, 10, 1984, 1984, {MDPI} {AG}, 02 Oct. 2021, [Peer-reviewed], [Corresponding author]
English, Scientific journal, We reported the genetic evidence of circulating hantaviruses from small mammals captured in a chronic kidney disease of unknown etiology (CKDu) hotspot area of Sri Lanka. The high seroprevalence of anti-hantavirus antibodies against Thailand orthohantavirus (THAIV) has been reported among CKDu patients and rodents in Sri Lankan CKDu hotspots. We captured 116 small mammals from CKDu endemic regions in the Polonnaruwa District of Sri Lanka. Seven animals (five out of 11 Mus booduga and two out of 99 Rattus rattus) were PCR-positive for the hantavirus. A rat-borne sequence was grouped with a THAIV-like Anjozorobe virus. In contrast, Mus-borne sequences belonged to the THAIV lineage, suggesting a novel orthohantavirus species according to the phylogenetic analyses and whole-genome comparisons. Our genetic evidence indicates the presence of two THAIV-related viruses circulating in this CKDu endemic area, suggesting a basis for further investigations to identify the infectious virus in patients with CKDu and the CKDu induction mechanism of these viruses.

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, 01 Jun. 2021, [Peer-reviewed], [Corresponding author], [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.

Immunological Responses to Seoul Orthohantavirus in Experimentally and Naturally Infected Brown Rats (Rattus norvegicus).
Shumpei P Yasuda, Kenta Shimizu, Takaaki Koma, Nguyen Thuy Hoa, Mai Quynh Le, Zhuoxing Wei, Devinda S Muthusinghe, Sithumini M W Lokupathirage, Futoshi Hasebe, Tetsu Yamashiro, Jiro Arikawa, Kumiko Yoshimatsu
Viruses, 13, 4, 12 Apr. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, To clarify the mechanism of Seoul orthohantavirus (SEOV) persistence, we compared the humoral and cell-mediated immune responses to SEOV in experimentally and naturally infected brown rats. Rats that were experimentally infected by the intraperitoneal route showed transient immunoglobulin M (IgM) production, followed by an increased anti-SEOV immunoglobulin G (IgG) antibody response and maturation of IgG avidity. The level of SEOV-specific cytotoxic T lymphocytes (CTLs) peaked at 6 days after inoculation and the viral genome disappeared from serum. In contrast, naturally infected brown rats simultaneously had a high rate of SEOV-specific IgM and IgG antibodies (28/43). Most of the IgM-positive rats (24/27) had the SEOV genome in their lungs, suggesting that chronic SEOV infection was established in those rats. In female rats with IgG avidity maturation, the viral load in the lungs was decreased. On the other hand, there was no relationship between IgG avidity and viral load in the lungs in male rats. A CTL response was not detected in naturally infected rats. The difference between immune responses in the experimentally and naturally infected rats is associated with the establishment of chronic infection in natural hosts.

U.S.-Japan cooperative medical sciences program: 22nd International Conference on Emerging Infectious Diseases in the Pacific Rim.
Kristina T Lu, Takuya Yamamoto, David McDonald, Wei Li, Marissa Tan, Meng Ling Moi, Eun-Chung Park, Kumiko Yoshimatsu, Marie Ricciardone, Allan Hildesheim, Yukari Totsuka, Asuka Nanbo, Opass Putcharoen, Gompol Suwanpimolkul, Watsamon Jantarabenjakul, Leilani Paitoonpong, F Gray Handley, K Gayle Bernabe, Masahiko Noda, Miwa Sonoda, Patrick Brennan, Diane E Griffin, Ichiro Kurane
Virology, 555, 71, 77, Mar. 2021, [International Magazine]
English, This review summarizes the presentations given at the 22nd International conference on Emerging Infectious Diseases in the Pacific Rim. The purpose of this annual meeting is to foster international collaborations and address important public health issues in the Asia-Pacific region. This meeting was held in Bangkok in February 2020 and focused on emerging virus infections. Unexpectedly, the SARS-CoV-2 pandemic was in the initial stages leading to a special session on COVID-19 in addition to talks on dengue, influenza, hepatitis, AIDS, Zika, chikungunya, rabies, cervical cancer and nasopharyngeal carcinoma.

Serological methods for detection of infection with shrew-borne hantaviruses: Thottapalayam, Seewis, Altai, and Asama viruses.
Zhouoxing Wei, Kenta Shimizu, Kumpei Nishigami, Yoshimi Tsuda, Yomani Sarathukumara, Devinda S Muthusinghe, Chandika D Gamage, Lishanta Granathne, Sithumini M W Lokupathirage, Nishanta Nanayakkara, Jiro Arikawa, Fuka Kikuchi, Keiko Tanaka-Taya, Motoi Suzuki, Shigeru Morikawa, Satoru Arai, Kumiko Yoshimatsu
Archives of virology, 166, 1, 275, 280, Jan. 2021, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, The infectivity of shrew-borne hantaviruses to humans is still unclear because of the lack of a serodiagnosis method for these viruses. In this study, we prepared recombinant nucleocapsid (rN) proteins of Seewis orthohantavirus, Altai orthohantavirus (ALTV), Thottapalayam thottimvirus (TPMV), and Asama orthohantavirus. Using monospecific rabbit sera, no antigenic cross-reactivity was observed. In a serosurvey of 104 samples from renal patients and 271 samples from heathy controls from Sri Lanka, one patient serum and two healthy control sera reacted with rN proteins of ALTV and TPMV, respectively. The novel assays should be applied to investigate potential infectivity of shrew-borne hantaviruses to humans.

The Polarity of an Amino Acid at Position 1891 of Severe Fever with Thrombocytopenia Syndrome Virus L Protein Is Critical for the Polymerase Activity.
Kisho Noda, Yoshimi Tsuda, Fumiya Kozawa, Manabu Igarashi, Kenta Shimizu, Jiro Arikawa, Kumiko Yoshimatsu
Viruses, 13, 1, 27 Dec. 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Severe fever with thrombocytopenia syndrome virus subclone B7 shows strong plaque formation and cytopathic effect induction compared with other subclones and the parental strain YG1. Compared to YG1 and the other subclones, only B7 possesses a single substitution in the L protein at the amino acid position 1891, in which N is changed to K (N1891K). In this study, we evaluate the effects of this mutation on L protein activity via a cell-based minigenome assay. Substitutions of N with basic amino acids (K or R) enhanced polymerase activity, while substitutions with an acidic amino acid (E) decreased this activity. Mutation to other neutral amino acids showed no significant effect on activity. These results suggest that the characteristic of the amino acid at position 1891 of the L protein are critical for its function, especially with respect to the charge status. Our data indicate that this C-terminal domain of the L protein may be crucial to its functions in genome transcription and viral replication.

Simultaneous serodetection of major rat infectious pathogens by a multiplex immunochromatographic assay.
Noriko Tosa, Tomoko Ishida, Kumiko Yoshimatsu, Nobuhito Hayashimoto, Kanae Shiokawa, Akira Takakura, Jiro Arikawa
Experimental animals, 12 Nov. 2020, [Peer-reviewed], [Corresponding author], [Domestic magazines]
English, Scientific journal, Rapid and simple serologic tests that require only a small amount of blood without the euthanization of animals are valuable for microbial control in colonies of laboratory animals. In this study, we developed a multiplex immunochromatographic assay (ICA) for detection of antibodies to Sendai virus (also known as hemagglutinating virus of Japan), hantavirus, and sialodacryoadenitis virus, which are causative agents of major infectious diseases in rats. For this assay, an ICA strip was placed into a microtube containing 150 μl PBS and either 0.75 μl of rat serum or 1.5 μl of whole blood. Binding antibodies were visualized by using anti-rat IgG antibody-conjugated colloidal gold. Under these conditions, the multiplex ICA simultaneously and specifically detected antibodies to multiple antigens. Positive serum samples for each infectious disease were used to evaluate the sensitivity and specificity of the multiplex ICA. The sensitivities of the multiplex ICA for Sendai virus, hantavirus, and sialodacryoadenitis virus were 100%, 100%, and 81%, respectively. No nonspecific reactions were observed in any of the 52 positive sera against heterologous antigens. In addition, 10 samples of uninfected sera did not show any bands except for the control line. These observations indicate high specificity of the multiplex ICA. Moreover, the multiplex ICA could be applied to diluted blood. These results indicate that the multiplex ICA is appropriate for rapid and simple serological testing of laboratory rats.

抗核蛋白質抗体を用いた各種ハンタウイルス抗原の新規検出法の確立　　　　　　　　　　　　　　　
三橋 健斗, 小林 進太郎, 好井 健太朗, 吉松 組子, 苅和 宏明
日本獣医学会学術集会講演要旨集, 163回, 253, 253, (公社)日本獣医学会, Oct. 2020
Japanese

Multilocus sequence typing reveals diverse known and novel genotypes of Leptospira spp. circulating in Sri Lanka.
Lilani Karunanayake, Chandika D Gamage, Chandima P Gunasekara, Sajiv De Silva, Hidemasa Izumiya, Masatomo Morita, Devinda S Muthusinghe, Kumiko Yoshimatsu, Roshan Niloofa, Panduka Karunanayake, Wimalasiri Uluwattage, Makoto Ohnishi, Nobuo Koizumi
PLoS neglected tropical diseases, 14, 8, e0008573, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Leptospirosis has gained much attention in Sri Lanka since its large outbreak in 2008. However, most of the cases were clinically diagnosed and information on Leptospira genotypes and serotypes currently prevailing in the country is lacking. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed 24 Leptospira strains from human patients as well as isolated and characterized three Leptospira strains from black rats using the microscopic agglutination test with antisera for 19 serovars and multilocus sequence typing. The isolates were identified as Leptospira borgpetersenii sequence types (STs) 143 and 144; L. interrogans STs 30, 34, 43, 44, 74, 75, 80, 308, 313, 314, 316, and 317; and L. kirschneri ST318. Six of the 15 STs were identified for the first time in this study. Five serogroups such as Autumnalis, Grippotyphosa, Hebdomadis, Javanica, and Pyrogenes were detected among the isolates. Contrary to previous studies, various genotypes including novel STs were isolated during an outbreak in Southern Province. L. borgpetersenii serogroup Javanica ST143 was isolated both from a human and black rat. CONCLUSIONS/SIGNIFICANCE: This study revealed that genetically diverse Leptospira strains currently circulate in Sri Lanka: some genotypes have been circulating and others have emerged recently, which may explain the recent surge of leptospirosis patients with varying clinical manifestations and frequent outbreaks of leptospirosis. Black rats were identified as the source of infection for humans, but reservoir animals for other genotypes remain unknown.

Species and genetic diversity of Bandicota (Murinae, Rodentia) from Myanmar based on mitochondrial and nuclear gene sequences
Satoko Mori, Thidalay Thwe, Wai Min Thu, Shumpei P. Yasuda, Saw Bawm, Kimiyuki Tsuchiya, Ken Katakura, Satoru Arai, Kumiko Yoshimatsu, Hitoshi Suzuki
Mammal Research, 65, 3, 493, 502, Springer Science and Business Media {LLC}, Jul. 2020, [Peer-reviewed]
English, Scientific journal

[Hantavirus infection as a risk for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka].
Kumiko Yoshimatsu
Uirusu, 70, 2, 175, 184, 2020, [Lead author, Corresponding author], [Domestic magazines]
Japanese, Scientific journal, Chronic kidney disease of unknown etiology (CKDu) has emerged in endemic areas of Sri Lanka since the 1990s. The disease is a chronic but fatal disease. Until now, heavy metals and agrochemicals have been suspected as the cause of CKDu, but it has been still unknown. Recently, we have found a high seroprevalence to hantavirus in CKDu patients and reported that hantavirus infection is a risk of CKDu. Hantaviruses are rodent-borne zoonotic viruses. Here, I would like to introduce a story of the research from sero-epidemiology to the search for host animals.

Reply to Comments by Yih et al. (Exposure to Hantavirus is a Risk Factor Associated with Kidney Diseases in Sri Lanka: A Cross-Sectional Study)
Y D Sarathkumara, Chandika Damesh Gamage, Sithumini Lokupathirage, Devinda S. Muthusinghe, Nishantha Nanayakkara, Lishanthe Gunarathne, Kenta Shimizu, Yoshimi Tsuda, Jiro Arikawa, Yoshimatsu
Viruses, 11, 8, 11 Dec. 2019, [Peer-reviewed], [Corresponding author]
Scientific journal

Multiplex Immunochromatographic Assay for Serologic Diagnosis of Major Infectious Diseases in Laboratory Mice.
Noriko Tosa, Tomoko Ishida, Kumiko Yoshimatsu, Nobuhito Hayashimoto, Kanae Shiokawa, Akira Takakura, Jiro Arikawa
Journal of the American Association for Laboratory Animal Science : JAALAS, 58, 6, 790, 795, 01 Nov. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Serologic monitoring of infectious diseases is important for microbial control in colonies of laboratory mice. Rapid and simple tests that do not require killing animals are valuable for this purpose. In this study, we developed a multiplex immunochromatographic assay (ICA) for detection of antibodies to mouse hepatitis virus (MHV), Sendai virus (also known as hemagglutinating virus of Japan [HVJ]), and Clostridium piliforme (The pathogen that causes Tyzzer disease), which are major infectious diseases in mice. For this assay, an ICA strip was put into a microtube containing 150 μL PBS and either 0.75 μL mouse serum or 1.5 μL whole blood. Binding antibodies were visualized by using protein A-conjugated colloidal gold. Under these conditions, multiplex ICA simultaneously and specifically detected antibodies to multiple antigens. To evaluate the sensitivity and specificity of multiplex ICA, positive serum samples for each infectious disease were used. Sensitivities of the multiplex ICA test for MHV, HVJ, and C. piliforme were 100%, 100%, and 90%, respectively. No nonspecific reaction was observed in any of the 30 positive sera. In addition, 10 samples of uninfected sera did not show any bands except for the control line. These observations indicate high specificity of the multiplex ICA test. Moreover, the multiplex ICA could be applied to diluted blood. These results indicate that the multiplex ICA is appropriate for rapid, simple, and safe serologic testing of laboratory mice.

Serological Evidence of Thailand Orthohantavirus or Antigenically Related Virus Infection Among Rodents in a Chronic Kidney Disease of Unknown Etiology Endemic Area, Girandurukotte, Sri Lanka
Lokupathirage, S.M.W., Muthusinghe, D.S., Shimizu, K., Nishigami, K., Noda, K., Tsuda, Y., Sarathkumara, Y.D., Gunawardana, S., Arikawa, J., Gamage, C.D., Yoshimatsu, K.
Vector-Borne and Zoonotic Diseases, 19, 11, Jul. 2019, [Peer-reviewed], [Corresponding author]
Scientific journal

Development of a multiplex immunochromatographic test for serological diagnosis of major infectious diseases in laboratory mice　　　　　　　　　　　　　　　
Tosa N, Ishida T, Yoshimatsu K, Hayashimoto N, Kanae S, Takakura A, Arikawa J
J Am Assoc Lab Anim Sci, Jun. 2019, [Peer-reviewed], [Corresponding author]

Thailand orthohantavirus infection in patients with chronic kidney disease of unknown aetiology in Sri Lanka
Yoshimatsu, K., Gamage, C.D., Sarathkumara, Y.D., Kulendiran, T., Muthusinghe, D.S., Nanayakkara, N., Gunarathne, L., Shimizu, K., Tsuda, Y., Arikawa, J.
Archives of Virology, 164, 1, 267, 271, Springer Science and Business Media {LLC}, 04 Jan. 2019, [Peer-reviewed], [Lead author, Corresponding author]
Scientific journal

Comparison of immune response in mice sensitized to an animal allergen, Can f 1, and to a food allergen, ovalbumin
Noriko Tosa, Kumiko Yoshimatsu, Motoko Takahashi, Jiro Arikawa
Biomedical Research, 40, 1, 9, 15, 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Can f 1 belongs to the lipocalin superfamily and is considered to be an animal allergen. The immune response induced by Can f 1 in mice was compared with that induced by ovalbumin (OVA), a typical food allergen. Female BALB/c and C57BL/6 mice (6 weeks of age) were subcutaneously injected with Can f 1 or OVA with or without aluminum hydroxide (Alum) three times with intervals of two weeks. Serum levels of total IgE or antigen-specific IgE and production of IL13 and IFNγ from splenocytes were analyzed. Immunization with Can f 1 or OVA increased serum levels of both total IgE and antigen-specific IgE significantly irrespective of Alum. These results indicate that Can f 1 and OVA were able to induce allergic sensitization in mice. Splenocyte production of IL13 in mice immunized with Can f 1 or OVA with and without Alum were significantly increased after stimulation with each antigen. However, IL13 levels in the mice immunized with Can f 1 with Alum were significantly lower than those immunized without Alum. Increases in IFNγ levels after stimulation with Can f 1 or OVA were not remarkable. No influence of genetic backgrounds of BALB/c and C57BL/6 mice was found. Although Can f 1 induced Th2 type immune responses as was also the case for immunization with OVA, an inhibitory effect of Alum on induction of IL13 was observed only in mice immunized with Can f 1. These results suggest that the immune mechanism for allergic sensitization with Can f 1 is different from that with OVA.

Development and evaluation of monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay for the diagnosis of acute leptospirosis in humans
Gamage, C., Sarathkumara, Y., Weerakkodi, V., Shiokawa, K., Yoshimatsu, K., Arikawa, J.
Journal of Immunological Methods, 463, 134, 136, Sep. 2018, [Peer-reviewed]
Scientific journal

Involvement of CD8+ T cells in the development of renal hemorrhage in a mouse model of hemorrhagic fever with renal syndrome
Kenta Shimizu, Kumiko Yoshimatsu, Midori Taruishi, Yoshimi Tsuda, Jiro Arikawa
Archives of Virology, 163, 6, 1577, 1584, Springer-Verlag Wien, 01 Jun. 2018, [Peer-reviewed]
English, Scientific journal

Expression of a Recombinant Nucleocapsid Protein of Rift Valley Fever Virus in Vero Cells as an Immunofluorescence Antigen and Its Use for Serosurveillance in Traditional Cattle Herds in Zambia
Ngonda Saasa, Masahiro Kajihara, George Dautu, Akina Mori-Kajihara, Shuetsu Fukushi, Yona Sinkala, Shigeru Morikawa, Aaron Mweene, Ayato Takada, Kumiko Yoshimatsu, Jiro Arikawa
Vector-Borne and Zoonotic Diseases, 18, 5, 273, 277, Mary Ann Liebert Inc., 01 May 2018, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Targeting of severe fever with thrombocytopenia syndrome virus structural proteins to the ERGIC (endoplasmic reticulum Golgi intermediate compartment) and Golgi complex
Tapiwa LUNDU, Yoshimi TSUDA, Ryo ITO, Kenta SHIMIZU, Shintaro KOBAYASHI, Kentaro YOSHII, Kumiko YOSHIMATSU, Jiro ARIKAWA, Hiroaki KARIWA
Biomedical Research, 39, 1, 27, 38, Biomedical Research Press, 2018, [Peer-reviewed]
Scientific journal

Establishment of Subclones of the Severe Fever with Thrombocytopenia Syndrome Virus YG1 Strain Selected Using Low pH-Dependent Cell Fusion Activity
Sanae Nishio, Yoshimi Tsuda, Ryo Ito, Kenta Shimizu, Kumiko Yoshimatsu, Jiro Arikawa
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 70, 4, 388, 393, Jul. 2017, [Peer-reviewed]
English, Scientific journal

Evidence of infection with Leptospira interrogans and spotted fever group rickettsiae among rodents in an urban area of Osaka City, Japan
Kenta Shimizu, Rie Isozumi, Kazutoshi Takami, Isao Kimata, Kanae Shiokawa, Kumiko Yoshimatsu, Yoshimi Tsuda, Sanae Nishio, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 7, 1261, 1263, Jul. 2017, [Peer-reviewed]
English, Scientific journal

Serological evidence of hantavirus infection in Girandurukotte, an area endemic for chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka
Chandika D. Gamage, Kumiko Yoshimatsu, Yomani D. Sarathkumara, Thiviyaaluxmi Kulendiran, Nishantha Nanayakkara, Jiro Arikawa
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 57, 77, 78, Apr. 2017, [Peer-reviewed], [Corresponding author]
English

Antibody detection from Middendorf's vole (Microtus middendorffii) against Tula virus captured in Mongolia
Kumiko Yoshimatsu, Satoru Arai, Kenta Shimizu, Yoshimi Tsuda, Bazartseren Boldgiv, Bazartseren Boldbaatar, Erdenebaatar Sergelen, Dagvatseren Ariunzaya, Orsoo Enkhmandal, Sukhbaatar Tuvshintugs, Shigeru Morikawa, Jiro Arikawa
JAPANESE JOURNAL OF VETERINARY RESEARCH, 65, 1, 39, 44, Feb. 2017, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Establishment of subclones of the severe fever with thrombocytopenia syndrome virus YG1 strain selected using low pH-dependent cell fusion activity
Sanae Nishio, Yoshimi Tsuda, Ryo Ito, Kenta Shimizu, Kumiko Yoshimatsu, Jiro Arikawa
Japanese Journal of Infectious Diseases, 70, 4, 388, 393, National Institute of Health, 2017, [Peer-reviewed]
English, Scientific journal

Epizootiological study of rodent-borne hepatitis E virus HEV-C1 in small mammals in Hanoi, Vietnam
Satomu Obana, Kenta Shimizu, Kumiko Yoshimatsu, Futoshi Hasebe, Kozue Hotta, Rie Isozumi, Hoa Thuy Nguyen, Mai Quynh Le, Tetsu Yamashiro, Yoshimi Tsuda, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 1, 76, 81, Jan. 2017, [Peer-reviewed]
English, Scientific journal

Appearance of renal hemorrhage in adult mice after inoculation of patient-derived hantavirus
Kenta Shimizu, Takaaki Koma, Kumiko Yoshimatsu, Yoshimi Tsuda, Yuji Isegawa, Jiro Arikawa
VIROLOGY JOURNAL, 14, 1, 13, Jan. 2017, [Peer-reviewed]
English, Scientific journal

The amino acid at position 624 in the glycoprotein of SFTSV (severe fever with thrombocytopenia virus) plays a critical role in low-pH-dependent cell fusion activity
Yoshimi Tsuda, Manabu Igarashi, Ryo Ito, Sanae Nishio, Kenta Shimizu, Kumiko Yoshimatsu, Jiro Arikawa
BIOMEDICAL RESEARCH-TOKYO, 38, 2, 89, 97, 2017, [Peer-reviewed]
English, Scientific journal

Serological evidence of infection with rodent-borne hepatitis E virus HEV-C1 or antigenically related virus in humans
Kenta Shimizu, Sugihiro Hamaguchi, Cuong Chi Ngo, Tian-Cheng Li, Shuji Ando, Kumiko Yoshimatsu, Shumpei P. Yasuda, Takaaki Koma, Rie Isozumi, Yoshimi Tsuda, Hiromi Fujita, Thuy Thanh Pham, Mai Quynh Le, Anh Duc Dang, Tuan Quang Nguyen, Lay-Myint Yoshida, Koya Ariyoshi, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 11, 1677, 1681, Nov. 2016, [Peer-reviewed]
English, Scientific journal

Identification of causative Leishmania species in Giemsa-stained smears prepared from patients with cutaneous leishmaniasis in Peru using PCR-RFLP
Yu Koarashi, Abraham G. Caceres, Florencia Margarita Zuniga Saca, Elsa Elvira Palacios Flores, Adela Celis Trujillo, Jose Luis Abanto Alvares, Kumiko Yoshimatsu, Jiro Arikawa, Ken Katakura, Yoshihisa Hashiguchi, Hirotomo Kato
ACTA TROPICA, 158, 83, 87, Jun. 2016, [Peer-reviewed]
English, Scientific journal

Evaluation of truncated LipL32 expressed by Escherichia coli and Pichia pastoris for serodiagnosis of Leptospira infection in rodents
Kanae Shiokawa, Chandika D. Gamage, Nobuo Koizumi, Yoshihiro Sakoda, Kenta Shimizu, Yoshimi Tsuda, Kumiko Yoshimatsu, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 78, 2, 221, 230, Feb. 2016, [Peer-reviewed]
English, Scientific journal

Multiple-locus variable-number tandem repeat analysis of Leptospira interrogans and Leptospira borgpetersenii isolated from small feral and wild mammals in East Asia
Nobuo Koizumi, Hidemasa Izumiya, Jung-Jung Mu, Zbigniew Arent, Shou Okano, Chie Nakajima, Yasuhiko Suzuki, Maki Mizutani Muto, Tsutomu Tanikawa, Kyle R. Taylor, Noriyuki Komatsu, Kumiko Yoshimatsu, Hoang Thi Thu Ha, Makoto Ohnishi
INFECTION GENETICS AND EVOLUTION, 36, 434, 440, Dec. 2015, [Peer-reviewed]
English, Scientific journal

First evidence of Seoul hantavirus in the wild rat population in the Netherlands
Jenny Verner-Carlsson, Mare Lõhmus, Karin Sundström, Tanja M. Strand, Monique Verkerk, Chantal Reusken, Kumiko Yoshimatsu, Jiro Arikawa, Frank van de Goot, Åke Lundkvist
African Journal of Disability, 5, 1, 27215, AOSIS OpenJournals Publishing AOSIS (Pty) Ltd, 2015, [Peer-reviewed]
English, Scientific journal

Distinct genetic characteristics of Sri Lankan Rattus and Bandicota (Murinae, Rodentia) inferred frommitochondrial and nuclear markers
Shumpei P. Yasuda, Chandika D. Gamage, Nobuo Koizumi, Sanae Nishio, Rie Isozumi, Kenta Shimizu, Takaaki Koma, Takako Amada, Hitoshi Suzuki, Kumiko Yoshimatsu, Jiro Arikawa
Genes and Genetic Systems, 89, 2, 71, 80, Genetics Society of Japan, 01 Sep. 2014, [Peer-reviewed]
English, Scientific journal

Antigenic Properties of N Protein of Hantavirus
Kumiko Yoshimatsu, Jiro Arikawa
VIRUSES-BASEL, 6, 8, 3097, 3109, Aug. 2014, [Peer-reviewed], [Lead author, Corresponding author]
English

Serological diagnosis with recombinant N antigen for hantavirus infection
Kumiko Yoshimatsu, Jiro Arikawa
VIRUS RESEARCH, 187, 77, 83, Jul. 2014, [Peer-reviewed]
English, Scientific journal

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice
Takaaki Koma, Kumiko Yoshimatsu, Noriyo Nagata, Yuko Sato, Kenta Shimizu, Shumpei P. Yasuda, Takako Amada, Sanae Nishio, Hideki Hasegawa, Jiro Arikawa
JOURNAL OF VIROLOGY, 88, 13, 7178, 7188, Jul. 2014, [Peer-reviewed]
English, Scientific journal

Development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses
Takako Amada, Kumiko Yoshimatsu, Takaaki Koma, Kenta Shimizu, Chandika D. Gamage, Kanae Shiokawa, Sanae Nishio, Clas Ahlm, Jiro Arikawa
VIROLOGY JOURNAL, 11, 87, May 2014, [Peer-reviewed]
English, Scientific journal

Role of nucleocapsid protein of hantaviruses in intracellular traffic of viral glycoproteins
Kenta Shimizu, Kumiko Yoshimatsu, Takaaki Koma, Shumpei P. Yasuda, Jiro Arikawa
Virus Research, 178, 2, 349, 356, 26 Dec. 2013, [Peer-reviewed]
English, Scientific journal

Rapid, whole blood diagnostic test for detecting anti-hantavirus antibody in rats
Takako Arnada, Kumiko Yoshimatsu, Shumpei P. Yasuda, Kenta Shimizu, Takaaki Koma, Nobuhito Hayashimoto, Chandika D. Gamage, Sanae Nishio, Akira Takakura, Jiro Arikawa
JOURNAL OF VIROLOGICAL METHODS, 193, 1, 42, 49, Oct. 2013, [Peer-reviewed]
English, Scientific journal

A survey of rodent-borne pathogens carried by wild Rattus spp. in Northern Vietnam
T. Koma, K. Yoshimatsu, S. P. Yasuda, T. Li, T. Amada, K. Shimizu, R. Isozumi, L. T.Q. Mai, N. T. Hoa, V. Nguyen, T. Yamashiro, F. Hasebe, J. Arikawa
Epidemiology and Infection, 141, 9, 1876, 1884, Sep. 2013, [Peer-reviewed]
English, Scientific journal

A survey of rodent-borne pathogens carried by wild Rattus spp. in Northern Vietnam
T. Koma, K. Yoshimatsu, S. P. Yasuda, T. Li, T. Amada, K. Shimizu, R. Isozumi, L. T.Q. Mai, N. T. Hoa, V. Nguyen, T. Yamashiro, F. Hasebe, J. Arikawa
Epidemiology and Infection, 141, 9, 1876, 1884, Sep. 2013, [Peer-reviewed]
English, Scientific journal

Epidemiology of Hantavirus Infection in Thousand Islands Regency of Jakarta, Indonesia
Ima-Nurisa Ibrahim, Kenta Shimizu, Kumiko Yoshimatsu, Andre Yunianto, Ervi Salwati, Shumpei P. Yasuda, Takaaki Koma, Rika Endo, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 75, 8, 1003, 1008, Aug. 2013, [Peer-reviewed]
English, Scientific journal

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

Characterization of Full Genome of Rat Hepatitis E Virus Strain from Vietnam
Tian-Cheng Li, Yasushi Ami, Yuriko Suzaki, Shumpei P. Yasuda, Kumiko Yoshimatsu, Jiro Arikawa, Naokazu Takeda, Wakita Takaji
EMERGING INFECTIOUS DISEASES, 19, 1, 115, 118, Jan. 2013, [Peer-reviewed]
English, Scientific journal

Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses
Tian-Cheng Li, Sayaka Yoshizaki, Yasushi Ami, Yuriko Suzaki, Shumpei P. Yasuda, Kumiko Yoshimatsu, Jiro Arikawa, Naokazu Takeda, Takaji Wakita
Veterinary Microbiology, 163, 1-2, 54, 61, 1-2, 2013, [Peer-reviewed]
English, Scientific journal

Introgressive hybridization of two major lineages of invasive Black Rats, Rattus rattus and R. tanezumi on the Japanese Islands inferred from Mc1r sequences
Kambe Yoshikazu, Suzuki Sosuke, Yabe Tatsuo, Nakata Katsushi, Maezono Yasunori, Abe Shintaro, Ishida Ken, Tanikawa Tsutomu, Hashimoto Takuma, Takeda Mikako, Tsuchiya Kimiyuki, Yoshimatsu Kumiko, Suzuki Hitoshi
Honyurui Kagaku (Mammalian Science), 53, 2, 289, 299, The Mammal Society of Japan, 2013
Japanese, Two invasive lineages of Black Rat (the Rattus rattus species complex) occur in Japan: the newly introduced Rattus rattus (2n=38) of Indian and European origin, and the anciently introduced R. tanezumi (2n=42) of East Asian origin. To assess the current distribution and invasion history of these lineages, we determined the nucleotide sequences of a coat color-related gene, melanocortin 1 receptor (Mc1r, 954 bp), in 36 rats from Japan and conducted phylogenetic analyses for a total of 133 rats mainly from Japan (17 localities). Mc1r haplotypes representing R. rattus were recovered from Otaru, the Ogasawara Islands, and Tokyo, and heterozygous individuals with the R. tanezumi type sequences were detected in these localities. These results imply that introgressive hybridization is currently going on in a variety of places in Japan such as urban and port areas, and on remote islands. In contrast, the R. rattus haplotypes were not detected in the natural forests of the Ryukyu Islands here represented by the islands of Amamioshima and Okinawa, implying the presence of some mechanism preventing the introduction of the invading lineage. We recovered some endemic haplotypes from the Ryukyu Islands, suggesting genetic differentiation between the Ryukyu Islands and other parts of Japan.

新世界ハンタウイルス感染のためのハンタウイルス組み換え核蛋白を用いた血清型鑑別ELISA法の開発　　　　　　　　　　　　　　　
駒 貴明, 吉松 組子, 垂石 みどり, 宮下 大輔, 遠藤 理香, 清水 健太, 安田 俊平, 天田 貴子, 瀬戸 隆, 村田 亮, 吉田 喜香, 苅和 宏明, 高島 郁夫, 有川 二郎
北海道医学雑誌, 88, 1, 35, 35, Jan. 2013
Japanese, Scientific journal

Variation in the bacterial conditions inside cages is correlated with intracage humidity and ammonia levels.　　　　　　　　　　　　　　　
Tosa N, Yoshimatsu K, Tadasuke Tsukiyama, Hatakeyama S, Arikawa J
Lab Animal and Environ, 21, 2, 87, 98, 2013, [Peer-reviewed]
English, Scientific journal

Negative Strand RNA Virusのウイルス学 7.ブニヤウイルスとその生態
吉松組子, 有川二郎
ウイルス, 62, 2, 239, 250, The Japanese Society for Virology, Dec. 2012
Japanese, The family Bunyaviridae consists of over 300 virus species and strains that are divided into 5 genera: orthobunyavirus, hantavirus, nairovirus, phlebovirus, and tospovirus. All members of family Bunyaviridae possess a negative-sense, single stranded tripartite RNA genome, consisting of large (L), medium (M) and small (S) segments, which encode an RNA-dependent RNA polymerase, two envelope glyoproteins (Gn and Gc) and nucleocapsid (N) protein, respectively. Insects and arthropods serve as vectors of viruses in the Bunyaviridae, except for hantviruses, which instead are harbored by rodents. However, phylogenetically distinct soricomorph-associated hantaviruses have been discovered in widely separated geographical regions spanning four continents. This new finding strongly suggests that evolutionary record of hantaviruses is far more complex and ancient than originally expected. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently described in northeast and central China. The causative agent of SFTS is phylogenetically classified to genus phlebivirus, but unlike to other member in genus phlebovirus, SFTV transmit by ticks. This review provides a brief overview of hantavirus and hantavirus infection and describes about two newly appeared viruses in the family Bunyaviridae.

Novel serological tools for detection of Thottapalayam virus, a Soricomorpha-borne hantavirus
Mathias Schlegel, Erdenesaikhan Tegshduuren, Kumiko Yoshimatsu, Rasa Petraityte, Kestutis Sasnauskas, Baerbel Hammerschmidt, Robert Friedrich, Marc Mertens, Martin H. Groschup, Satoru Arai, Rika Endo, Kenta Shimizu, Takaaki Koma, Shumpei Yasuda, Chiaki Ishihara, Rainer G. Ulrich, Jiro Arikawa, Bernd Koellner
ARCHIVES OF VIROLOGY, 157, 11, 2179, 2187, Nov. 2012, [Peer-reviewed]
English, Scientific journal

Development of a serotyping enzyme-linked immunosorbent assay system based on recombinant truncated hantavirus nucleocapsid proteins for New World hantavirus infection
Takaaki Koma, Kumiko Yoshimatsu, Midori Taruishi, Daisuke Miyashita, Rika Endo, Kenta Shimizu, Shumpei P. Yasuda, Takako Amada, Takahiro Seto, Ryo Murata, Haruka Yoshida, Hiroaki Kariwa, Ikuo Takashima, Jiro Arikawa
JOURNAL OF VIROLOGICAL METHODS, 185, 1, 74, 81, Oct. 2012, [Peer-reviewed]
English, Scientific journal

Isolation of Hokkaido virus, genus Hantavirus, using a newly established cell line derived from the kidney of the grey red-backed vole (Myodes rufocanus bedfordiae)
Takahiro Sanada, Takahiro Seto, Yuka Ozaki, Ngonda Saasa, Kumiko Yoshimatsu, Jiro Arikawa, Kentaro Yoshii, Hiroaki Kariwa
JOURNAL OF GENERAL VIROLOGY, 93, 10, 2237, 2246, Oct. 2012, [Peer-reviewed]
English, Scientific journal

Development of a Diagnostic Method Applicable to Various Serotypes of Hantavirus Infection in Rodents
Takahiro Sanada, Hiroaki Kariwa, Ngonda Saasa, Keisuke Yoshikawa, Takahiro Seto, Vyacheslav G. Morozov, Evgeniy A. Tkachenko, Leonid I. Ivanov, Kumiko Yoshimatsu, Jiro Arikawa, Kentaro Yoshii, Ikuo Takashima
JOURNAL OF VETERINARY MEDICAL SCIENCE, 74, 9, 1237, 1242, Sep. 2012, [Peer-reviewed]
English, Scientific journal

Studies on Hantavirus Infection in Small Mammals Captured in Southern and Central Highland Area of Vietnam
Vu Dinh Luan, Kumiko Yoshimatsu, Rika Endo, Midori Taruishi, Vo Thi Huong, Dang Tuan Dat, Pham Cong Tien, Kenta Shimzu, Takaaki Koma, Shumpei P. Yasuda, Le Nhi, Vu Thi Que Huong, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 74, 9, 1155, 1162, Sep. 2012, [Peer-reviewed]
English, Scientific journal

Ecology of hantaviruses in Mexico: Genetic identification of rodent host species and spillover infection
Ngonda Saasa, Cornelio Sanchez-Hernandez, Maria de Lourdes Romero-Almaraz, Ezequiel Guerrero-Ibarra, Alberto Almazan-Catalan, Haruka Yoshida, Daisuke Miyashita, Mariko Ishizuka, Takahiro Sanada, Takahiro Seto, Kentaro Yoshii, Celso Ramos, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima, Hiroaki Kariwa
VIRUS RESEARCH, 168, 1-2, 88, 96, Sep. 2012, [Peer-reviewed]
English, Scientific journal

ベトナムのラットおよびヒトにおけるラットE型肝炎ウイルスの感染状況の調査　　　　　　　　　　　　　　　
清水 健太, 李 天成, 安田 俊平, 吉松 組子, 駒 貴明, 長谷部 太, 山城 哲, Hoa Nguyen Thuy, Mai Le Thi Quynh, 有川 二郎
日本獣医学会学術集会講演要旨集, 154回, 265, 265, (公社)日本獣医学会, Aug. 2012
Japanese

新たに分離されたHokkaidoウイルスの性状解析　　　　　　　　　　　　　　　
真田 崇弘, 尾崎 由佳, 瀬戸 隆弘, 中尾 桃子, Saasa Ngonda, 吉松 組子, 有川 二郎, 好井 健太朗, 苅和 宏明
日本獣医学会学術集会講演要旨集, 154回, 265, 265, (公社)日本獣医学会, Aug. 2012, [Peer-reviewed]
Japanese

bla(NDM-1)-positive Klebsiella pneumoniae from Environment, Vietnam
Rie Isozumi, Kumiko Yoshimatsu, Tetsu Yamashiro, Futoshi Hasebe, Binh Minh Nguyen, Tuan Cuong Ngo, Shumpei P. Yasuda, Takaaki Koma, Kenta Shimizu, Jiro Arikawa
EMERGING INFECTIOUS DISEASES, 18, 8, 1383, 1385, Aug. 2012, [Peer-reviewed]
English

The N-terminus of the Montano virus nucleocapsid protein possesses broadly cross-reactive conformation-dependent epitopes conserved in rodent-borne hantaviruses
Ngonda Saasa, Haruka Yoshida, Kenta Shimizu, Cornelio Sanchez-Hernandez, Maria de Lourdes Romero-Almaraz, Takaaki Koma, Takahiro Sanada, Takahiro Seto, Kentaro Yoshii, Celso Ramos, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima, Hiroaki Kariwa
VIROLOGY, 428, 1, 48, 57, Jun. 2012, [Peer-reviewed]
English, Scientific journal

腎症候性出血熱の動物モデルの開発　　　　　　　　　　　　　　　
清水 健太, 吉松 組子, 駒 貴明, 伊勢川 裕二, 安田 俊平, 天田 貴子, 五十棲 理恵, 有川 二郎
日本獣医学会学術集会講演要旨集, 153回, 247, 247, (公社)日本獣医学会, Mar. 2012
Japanese

イムノクロマト法による抗ハンタウイルス抗体の迅速抗体検出法の開発　　　　　　　　　　　　　　　
天田 貴子, 吉松 組子, 安田 俊平, 駒 貴明, 清水 健太, 五十棲 理恵, 林元 展人, 高倉 彰, 有川 二郎
日本獣医学会学術集会講演要旨集, 153回, 273, 273, (公社)日本獣医学会, Mar. 2012
Japanese

Isolation and Characterization of Hantaviruses in Far East Russia and Etiology of Hemorrhagic Fever with Renal Syndrome in the Region
Hiroaki Kariwa, Keisuke Yoshikawa, Yoichi Tanikawa, Takahiro Seto, Takahiro Sanada, Ngonda Saasa, Leonid I. Ivanov, Raisa Slonova, Tatyana A. Zakharycheva, Ichiro Nakamura, Kumiko Yoshimatsu, Jiro Arikawa, Kentaro Yoshii, Ikuo Takashima
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 86, 3, 545, 553, Mar. 2012, [Peer-reviewed]
English, Scientific journal

Application of Truncated Nucleocapsid Protein (N) for Serotyping ELISA of Murinae-Associated Hantavirus Infection in Rats
Shumpei P. Yasuda, Kumiko Yoshimatsu, Takaaki Koma, Kenta Shimizu, Rika Endo, Rie Isozumi, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 74, 2, 215, 219, Feb. 2012, [Peer-reviewed]
English, Scientific journal

Genetic diversity of hantaviruses in Mexico: Identification of three novel hantaviruses from Neotominae rodents
Hiroaki Kariwa, Haruka Yoshida, Cornelio Sanchez-Hernandez, Maria de Lourdes Romero-Almaraz, Jose Alberto Almazan-Catalan, Celso Ramos, Daisuke Miyashita, Takahiro Seto, Ayako Takano, Masashi Totani, Ryo Murata, Ngonda Saasa, Mariko Ishizuka, Takahiro Sanada, Kentaro Yoshii, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima
VIRUS RESEARCH, 163, 2, 486, 494, Feb. 2012, [Peer-reviewed]
English, Scientific journal

Outbreak of Leptospirosis after Flood, the Philippines, 2009
Al-shere T. Amilasan, Mugen Ujiie, Motoi Suzuki, Eumelia Salva, Maria Cecilia P. Belo, Nobuo Koizumi, Kumiko Yoshimatsu, Wolf-Peter Schmidt, Shane Marte, Efren M. Dimaano, Jose Benito Villarama, Koya Ariyoshi
EMERGING INFECTIOUS DISEASES, 18, 1, 91, 94, Jan. 2012, [Peer-reviewed]
English, Scientific journal

[Bunyavirus and its ecology].
Yoshimatsu, K., Arikawa, J.
Uirusu, 62, 2, 239, 250, 2012, [Peer-reviewed]
Scientific journal

Characterization of self-assembled virus-like particles of rat hepatitis E virus generated by recombinant baculoviruses
Tian-Cheng Li, Kumiko Yoshimatsu, Shumpei P. Yasuda, Jiro Arikawa, Takaaki Koma, Michiyo Kataoka, Yasushi Ami, Yuriko Suzaki, Le Thi Quynh Mai, Nguyen Thuy Hoa, Tetsu Yamashiro, Futoshi Hasebe, Naokazu Takeda, Takaji Wakita
JOURNAL OF GENERAL VIROLOGY, 92, Pt 12, 2830, 2837, Dec. 2011, [Peer-reviewed]
English, Scientific journal

Effect of environmental enrichment after the occurrence of wet bedding created by mice and abnormal fur in mice.　　　　　　　　　　　　　　　
Tosa N, Yoshimatsu K, Arikawa J
J Am Assoc Lab Anim Sci, 50, 5, 779, 780, Sep. 2011, [Peer-reviewed]

Puumala virus infection in Syrian hamsters (Mesocricetus auratus) resembling hantavirus infection in natural rodent hosts
Takahiro Sanada, Hiroaki Kariwa, Noriyo Nagata, Yoichi Tanikawa, Takahiro Seto, Kumiko Yoshimatsu, Jiro Arikawa, Kentaro Yoshii, Ikuo Takashima
VIRUS RESEARCH, 160, 1-2, 108, 119, Sep. 2011, [Peer-reviewed]
English, Scientific journal

ハンタウイルス糖蛋白質の細胞内輸送に関与するウイルス蛋白質とその機能領域　　　　　　　　　　　　　　　
清水 健太, 吉松 組子, 駒 貴明, 安田 俊平, 有川 二郎
日本獣医学会学術集会講演要旨集, 152回, 236, 236, (公社)日本獣医学会, Aug. 2011
Japanese

日本のげっ歯類のハンタウイルス感染状況に関する血清疫学調査とエゾヤチネズミが保有するHokkaidoウイルスの遺伝的多様性　　　　　　　　　　　　　　　
尾崎 由佳, 萩谷 友洋, 真田 崇弘, 瀬戸 隆弘, Kyle Taylor, 吉川 佳佑, Leonid Ivanov, 好井 健太朗, 坪田 敏男, 池中 良徳, 石塚 真由美, 吉松 組子, 有川 二郎, 苅和 宏明
日本獣医学会学術集会講演要旨集, 152回, 256, 256, (公社)日本獣医学会, Aug. 2011, [Peer-reviewed]
Japanese

日本のげっ歯類のハンタウイルス感染状況に関する血清疫学調査とエゾヤチネズミが保有するHokkaidoウイルスの遺伝的多様性
尾崎由佳, 萩谷友洋, 真田崇弘, 瀬戸隆弘, TAYLOR Kyle, 吉川佳佑, IVANOV Leonid I, 好井健太朗, 坪田敏男, 池中良徳, 石塚真由美, 吉松組子, 有川二郎, 苅和宏明
北海道獣医師会雑誌, 55, 8, 415, 415, (公社)北海道獣医師会, Aug. 2011
Japanese

Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51
Kazuhiko Ochiai, Yasunaga Yoshikawa, Kumiko Yoshimatsu, Toshina Oonuma, Yukiko Tomioka, Eichi Takeda, Jiro Arikawa, Katsumi Mominoki, Toshinori Omi, Kazuyoshi Hashizume, Masami Morimatsu
FEBS LETTERS, 585, 12, 1771, 1777, Jun. 2011, [Peer-reviewed]
English, Scientific journal

An efficient in vivo method for the isolation of Puumala virus in Syrian hamsters and the characterization of the isolates from Russia
Takahiro Seto, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Yoichi Tanikawa, Sergey I. Kolominov, Sergey N. Belov, Ichiro Nakamura, Nobuo Hashimoto, Yasuhiro Kon, Alexander E. Balakiev, Tamara K. Dzagurnova, Olga A. Medvedkina, Mina Nakauchi, Mariko Ishizuka, Kentaro Yoshii, Kumiko Yoshimatsu, Leonid V. Ivanov, Jiro Arikawa, Ikuo Takashima, Hiroaki Kariwa
JOURNAL OF VIROLOGICAL METHODS, 173, 1, 17, 23, Apr. 2011, [Peer-reviewed]
English, Scientific journal

Serological Evidence of Thailand Virus-Related Hantavirus Infection among Suspected Leptospirosis Patients in Kandy, Sri Lanka
Chandika D. Gamage, Shumpei P. Yasuda, Sanae Nishio, Senanayake A. Kularatne, Kosala Weerakoon, Jayanthe Rajapakse, Chinyere Nwafor-Okoli, Romeo B. Lee, Yoshi Obayashi, Kumiko Yoshimatsu, Jiro Arikawa, Hiko Tamashiro
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 64, 1, 72, 75, Jan. 2011
English, Scientific journal

Serological Evidence of Thailand Virus-Related Hantavirus Infection among Suspected Leptospirosis Patients in Kandy, Sri Lanka
Chandika D. Gamage, Shumpei P. Yasuda, Sanae Nishio, Senanayake A. Kularatne, Kosala Weerakoon, Jayanthe Rajapakse, Chinyere Nwafor-Okoli, Romeo B. Lee, Yoshi Obayashi, Kumiko Yoshimatsu, Jiro Arikawa, Hiko Tamashiro
JAPANESE JOURNAL OF INFECTIOUS DISEASES, 64, 1, 72, 75, Jan. 2011, [Peer-reviewed]
English, Scientific journal

Different cross-reactivity of human and rodent sera to Tula virus and Puumala virus
Erdenesaikhan Tegshduuren, Kumiko Yoshimatsu, Midori Taruishi, Rika Endo, Kenta Shimizu, Takaaki Koma, Shumpei P. Yasuda, Hiroaki Kariwa, Jiro Arikawa, Chiaki Ishihara
COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 33, 6, E67, E73, Dec. 2010, [Peer-reviewed]
English, Scientific journal

ハンタウイルスNucleocapsid proteinはGlycoprotein Gcのシスゴルジへの局在を促進する　　　　　　　　　　　　　　　
清水 健太, 吉松 組子, 駒 貴明, 遠藤 理香, 安田 俊平, Erdenesaikhan Tegshduuren, 有川 二郎
日本獣医学会学術集会講演要旨集, 150回, 232, 232, (公社)日本獣医学会, Sep. 2010
Japanese

メキシコ由来のハンタウイルスに対するモノクローナル抗体の作出と各種ハンタウイルスに対する反応性の検討　　　　　　　　　　　　　　　
吉田 喜香, 苅和 宏明, 真田 崇弘, Saasa Ngonda, 瀬戸 隆弘, 吉松 組子, 有川 二郎, 好井 健太朗, 高島 郁夫
日本獣医学会学術集会講演要旨集, 150回, 249, 249, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
Japanese

Puumalaウイルスを感染させたシリアンハムスター(Mesocricetus auratus)の感染動態の解析　　　　　　　　　　　　　　　
真田 崇弘, 苅和 宏明, 谷川 洋一, Nur Hardy Abu Daud, 瀬戸 隆弘, 永田 典代, 吉松 組子, 有川 二郎, 好井 健太朗, 高島 郁夫
日本獣医学会学術集会講演要旨集, 150回, 252, 252, (公社)日本獣医学会, Sep. 2010, [Peer-reviewed]
Japanese

Truncated Hantavirus Nucleocapsid Proteins for Serotyping Sin Nombre, Andes, and Laguna Negra Hantavirus Infections in Humans and Rodents
Takaaki Koma, Kumiko Yoshimatsu, Noemi Pini, David Safronetz, Midori Taruishi, Silvana Levis, Rika Endo, Kenta Shimizu, Shumpei P. Yasuda, Hideki Ebihara, Heinz Feldmann, Delia Enria, Jiro Arikawa
JOURNAL OF CLINICAL MICROBIOLOGY, 48, 5, 1635, 1642, May 2010, [Peer-reviewed]
English, Scientific journal

Hemorrhagic Fever with Renal Syndrome, Vietnam
Vu Thi Que Huong, Kumiko Yoshimatsu, Vu Dinh Luan, Le Van Tuan, Le Nhi, Jiro Arikawa, Tran Minh Nhu Nguyen
EMERGING INFECTIOUS DISEASES, 16, 2, 363, 365, Feb. 2010, [Peer-reviewed]
English

Extensive Host Sharing of Central European Tula Virus
Jonas Schmidt-Chanasit, Sandra Essbauer, Rasa Petraityte, Kumiko Yoshimatsu, Kirsten Tackmann, Franz J. Conraths, Kestutis Sasnauskas, Jiro Arikawa, Astrid Thomas, Martin Pfeffer, Jerrold J. Scharninghausen, Wolf Splettstoesser, Matthias Wenk, Gerald Heckel, Rainer G. Ulrich
JOURNAL OF VIROLOGY, 84, 1, 459, 474, Jan. 2010, [Peer-reviewed]
English, Scientific journal

Epidemiological Study of Hantavirus Infection in the Samara Region of European Russia
Hiroaki Kariwa, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Takahiro Seto, Yoichi Tanikawa, Sergey I. Kolominov, Sergey N. Belov, Ichiro Nakamura, Nobuo Hashimoto, Alexander E. Balakiev, Tamara K. Dzagurnova, Nur Hardy bin Abu Daud, Daisuke Miyashita, Olga A. Medvedkina, Mina Nakauchi, Mariko Ishizuka, Kentaro Yoshii, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima
JOURNAL OF VETERINARY MEDICAL SCIENCE, 71, 12, 1569, 1578, Dec. 2009, [Peer-reviewed]
English, Scientific journal

Molecular Epidemiological and Serological Studies of Hantavirus Infection in Northern Vietnam
Thua Thang Truong, Kumiko Yoshimatsu, Koichi Araki, Byoung-Hee Lee, Ichiro Nakamura, Rika Endo, Kenta Shimizu, Shumpei P. Yasuda, Takaaki Koma, Midori Taruishi, Megumi Okumura, Uyen Ninh Truong, Jiro Arikawa
JOURNAL OF VETERINARY MEDICAL SCIENCE, 71, 10, 1357, 1363, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Hantavirus species in India : A retrospective study
S. Chandy, M. Okumura, K. Yoshimatsu, R. G. Ulrich, G. T. John, P. Abraham, J. Arikawa, G. Sridharan
INDIAN JOURNAL OF MEDICAL MICROBIOLOGY, 27, 4, 348, 350, Oct. 2009
English, Scientific journal

メキシコの野生げっ歯類が保有するハンタウイルスの遺伝子解析　　　　　　　　　　　　　　　
吉田 喜香, 苅和 宏明, 高野 絢子, 戸谷 理詩, 宮下 大輔, Ngonda Saasa, 瀬戸 隆弘, 真田 崇弘, 吉川 佳佑, 好井 健太朗, 吉松 組子, 有川 次郎, 高島 郁夫
日本獣医学会学術集会講演要旨集, 148回, 237, 237, (公社)日本獣医学会, Sep. 2009, [Peer-reviewed]
Japanese

極東ロシアの野鼠からのハンタウイルスの分離と人におけるウイルス感染状況の調査　　　　　　　　　　　　　　　
吉川 佳佑, 苅和 宏明, 瀬戸 隆弘, 真田 崇弘, 石塚 万里子, 吉松 組子, 有川 二郎, Ivanov Leonid, Slonova Raisa, 好井 健太朗, 高島 郁夫
北海道獣医師会雑誌, 53, 8, 112, 112, (公社)北海道獣医師会, Aug. 2009, [Peer-reviewed]
Japanese

Seroepidemiological study in a Puumala virus outbreak area in South-East Germany
Marc Mertens, Roman Woelfel, Katrin Ullrich, Kumiko Yoshimatsu, Jana Blumhardt, Ina Roemer, Jutta Esser, Jonas Schmidt-Chanasit, Martin H. Groschup, Gerhard Dobler, Sandra S. Essbauer, Rainer G. Ulrich
MEDICAL MICROBIOLOGY AND IMMUNOLOGY, 198, 2, 83, 91, May 2009, [Peer-reviewed]
English, Scientific journal

Acute febrile illness caused by hantavirus: serological and molecular evidence from India
Sara Chandy, Kumiko Yoshimatsu, Hari Kishan Boorugu, Anugrah Chrispal, Kurien Thomas, Abraham Peedicayil, Priya Abraham, Jiro Arikawa, Gopalan Sridharan
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 103, 4, 407, 412, Apr. 2009, [Peer-reviewed]
English, Scientific journal

極東ロシアのげっ歯類からのハンタウイルスの分離とウイルス遺伝子の性状解析　　　　　　　　　　　　　　　
吉川 佳佑, 苅和 宏明, 瀬戸 隆弘, 真田 崇弘, 石塚 万里子, 吉松 組子, 有川 二郎, Ivanov Lenid, 好井 健太朗, 高島 郁夫
日本獣医学会学術集会講演要旨集, 147回, 260, 260, (公社)日本獣医学会, Mar. 2009, [Peer-reviewed]
Japanese

Genetic and antigenic analyses of a Puumala virus isolate as a potential vaccine strain
Nur Hardy Abu Daud, Hiroaki Kariwa, Evgeniy Tkachenko, Tamara Dzagurnova, Olga Medvedkina, Petr Tkachenko, Mariko Ishizuka, Takahiro Seto, Daisuke Miyashita, Takahiro Sanada, Mina Nakauchi, Kentaro Yoshii, Akihiko Maeda, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima
JAPANESE JOURNAL OF VETERINARY RESEARCH, 56, 3, 151, 165, Nov. 2008, [Peer-reviewed]
English, Scientific journal

多種類のハンタウイルス血清型の検出が可能な抗原検出法の開発　　　　　　　　　　　　　　　
真田 崇弘, 苅和 宏明, 瀬戸 隆弘, 谷川 洋一, 宮下 大輔, 吉松 組子, 有川 二郎, 好井 健太朗, 高島 郁夫
日本獣医学会学術集会講演要旨集, 146回, 225, 225, (公社)日本獣医学会, Sep. 2008, [Peer-reviewed]
Japanese

Lack of vertical transmission of Hantaan virus from persistently infected dam to progeny in laboratory mice
Midori Taruishi, Kumiko Yoshimatsu, Rei Hatsuse, Megumi Okumura, Ichiro Nakamura, Jiro Arikawa
ARCHIVES OF VIROLOGY, 153, 8, 1605, 1609, Aug. 2008, [Peer-reviewed]
English, Scientific journal

Development of a serotyping ELISA system for Thailand virus infection
Ichiro Nakamura, Kumiko Yoshimatsu, Byoung-Hee Lee, Megumi Okumura, Midori Taruishi, Koichi Araki, Hiroaki Kariwa, Ikuo Takashima, Jiro Arikawa
ARCHIVES OF VIROLOGY, 153, 8, 1537, 1542, Aug. 2008, [Peer-reviewed]
English, Scientific journal

Arch Virol　　　　　　　　　　　　　　　
Nakamura, I, Yoshimatsu, K, Lee, B. H, Okumura, M, Taruishi, M, Araki, K, Kariwa, H, Takashima, I, Arikawa, J
Development of a serotyping ELISA system for Thailand virus infection., 153, 1537, 1542, 2008

Seroepidemiological study on hantavirus infections in India
Sara Chandy, Kumiko Yoshimatsu, Rainer G. Ulrich, Marc Mertens, Megumi Okumura, P. Rajendran, George T. John, Vinohar Balraj, Jayaprakash Muliyil, Joy Mammen, Priya Abraham, Jiro Arikawa, Gopalan Sridharan
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 102, 1, 70, 74, Jan. 2008, [Peer-reviewed]
English, Scientific journal

Analysis of the immune response of Hantaan virus nucleocapsid protein-specific CD8+ T cells in mice
Midori Taruishi, Kumiko Yoshimatsu, Koichi Araki, Megumi Okumura, Ichiro Nakamura, Kilchl Kajino, Jiro Arikawa
VIROLOGY, 365, 2, 292, 301, Sep. 2007, [Peer-reviewed]
English, Scientific journal

Hantavirus infection in East Asia
Hiroaki Kariwa, Kumiko Yoshimatsu, Jiro Arikawa
COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 30, 5-6, 341, 356, Sep. 2007, [Peer-reviewed]
French, Scientific journal

Hantavirus Infection - typical rodent-borne viral zoonosis.
Arikawa J, Yoshimatsu K, Truong UT, Troung UN
Trop Med Health, 35, 2, 55, 59, Japanese Society of Tropical Medicine, Sep. 2007, [Peer-reviewed]
English

Prevalence of antibody to hepatitis E virus among wild sika deer, Cervus nippon, in Japan
Y. Matsuura, M. Suzuki, K. Yoshimatsu, J. Arikawa, I. Takashima, M. Yokoyama, H. Igota, K. Yamauchi, S. Ishida, D. Fukui, G. Bando, M. Kosuge, H. Tsunemitsu, C. Koshimoto, K. Sakae, M. Chikahira, S. Ogawa, T. Miyamura, N. Takeda, T. C. Li
ARCHIVES OF VIROLOGY, 152, 7, 1375, 1381, Jul. 2007
English, Scientific journal

Development of serological assays for Thottapalayam virus, an insectivore-borne Hantavirus
Megumi Okumura, Kumiko Yoshimatsu, Sanit Kumperasart, Ichiro Nakamura, Michiko Ogino, Midori Taruishi, Araya Sungdee, Sirima Pattamadilok, Ima Nurisa Ibrahim, Sri Erlina, Takashi Agui, Richard Yanagihara, Jiro Arikawa
CLINICAL AND VACCINE IMMUNOLOGY, 14, 2, 173, 181, Feb. 2007, [Peer-reviewed]
English, Scientific journal

A comparative epidemiological study of hantavirus infection in Japan and Far East Russia
Hiroaki Kariwa, Kumari Lokugamage, Nandadeva Lokugamage, Hironobu Miyamoto, Kentaro Yoshii, Mina Nakauchi, Kumiko Yoshimatsu, Jiro Arikawa, Leonid I. Ivanov, Takuya Iwasaki, Ikuo Takashima
JAPANESE JOURNAL OF VETERINARY RESEARCH, 54, 4, 145, 161, Feb. 2007, [Peer-reviewed]
English

Mode of infection of Hokkaido virus (Genus hantavirus) among grey red-backed voles, Myodes rufocanus, in Hokkaido, Japan
Nur Hardy Abu Daud, Hiroaki Kariwa, Yoich Tanikawa, Ichiro Nakamura, Takahiro Seto, Daisuke Miyashita, Kentaro Yoshii, Mina Nakauchi, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima
MICROBIOLOGY AND IMMUNOLOGY, 51, 11, 1081, 1090, 2007, [Peer-reviewed]
English, Scientific journal

Geographical distribution of hantaviruses in Thailand and potential human health significance of Thailand virus
Sirima Pattamadilok, Byoung-Hee Lee, Sanit Kumperasart, Kumiko Yoshimatsu, Megumi Okumura, Ichiro Nakamura, Koichi Araki, Yuvaluk Khoprasert, Prayadh Dangsupa, Pornpitak Panlar, Burkhard Jandrig, Detlev H. Krueger, Boris Klempa, Thomas Jaekel, Jonas Schmidt, Rainer Ulrich, Hiroaki Kariwa, Jiro Arikawa
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 75, 5, 994, 1002, Nov. 2006, [Peer-reviewed]
English, Scientific journal

A pseudotype vesicular stomatitis virus containing Hantaan virus envelope glycoproteins G1 and G2 as an alternative to hantavirus vaccine in mice
BH Lee, K Yoshimatsu, K Araki, M Okumura, Nakamura, I, J Arikawa
VACCINE, 24, 15, 2928, 2934, Apr. 2006
English, Scientific journal

A pseudotype vesicular stomatitis virus containing Hantaan virus envelope glycoproteins G1 and G2 as an alternative to hantavirus vaccine in mice
BH Lee, K Yoshimatsu, K Araki, M Okumura, Nakamura, I, J Arikawa
VACCINE, 24, 15, 2928, 2934, Apr. 2006, [Peer-reviewed]
English, Scientific journal

Soochong virus: An antigenically and genetically distinct hantavirus isolated from Apodemus peninsulae in Korea
LJ Baek, H Kariwa, K Lokugamage, K Yoshimatsu, J Arikawa, Takashima, I, JI Kang, SS Moon, SY Chung, EJ Kim, HJ Kang, KJ Song, TA Klein, R Yanagihara, JW Song
JOURNAL OF MEDICAL VIROLOGY, 78, 2, 290, 297, Feb. 2006, [Peer-reviewed]
English, Scientific journal

A pilot study for serological evidence of hantavirus infection in human population in south India
S Chandy, S Mitra, N Sathish, TS Vijayakumar, OC Abraham, MV Jesudason, P Abraham, K Yoshimatsu, J Arikawa, G Sridharan
INDIAN JOURNAL OF MEDICAL RESEARCH, 122, 3, 211, 215, Sep. 2005, [Peer-reviewed]
English, Scientific journal

野生げっ歯類からのハンタウイルス抗原検出用ELISAの開発　　　　　　　　　　　　　　　
谷川 洋一, 苅和 宏明, 萩谷 友洋, Lokugamage Nandadeva, Lokugamage Kumari, 舘 敦史, 好井 健太朗, 吉松 組子, 有川 二郎, 高島 郁夫
日本獣医学会学術集会講演要旨集, 139回, 185, 185, (公社)日本獣医学会, Mar. 2005, [Peer-reviewed]
Japanese

Nucleocapsid protein of cell culture-adapted Seoul virus strain 80-39: Analysis of its encoding sequence, expression in yeast and immuno-reactivity
Jonas Schmidt, Burkhard Jandrig, Boris Klempa, Kumiko Yoshimatsu, Jiro Arikawa, Helga Meisel, Matthias Niedrig, Christian Pitra, Detlev H. Krüger, Rainer Ulrich
Virus Genes, 30, 1, 37, 48, Jan. 2005
English, Scientific journal

Nucleocapsid protein of cell culture-adapted Seoul virus strain 80-39: Analysis of its encoding sequence, expression in yeast and immuno-reactivity
J Schmidt, B Jandrig, B Klempa, K Yoshimatsu, J Arikawa, H Meisel, M Niedrig, C Pitra, DH Kruger, R Ulrich
VIRUS GENES, 30, 1, 37, 48, Jan. 2005, [Peer-reviewed]
English, Scientific journal

A pilot study for serological evidence of hantavirus infection in human population in south India　　　　　　　　　　　　　　　
Chandy, S, Mitra, S, Sathish, N, Vijayakumar, T. S, Abraham, O. C, Jesudason, M. V, Abraham, P, Yoshimatsu, K, Arikawa, J, Sridharan, G
Indian J Med Res, 122, 211, 215, 2005

Epitope analysis of monoclonal antibody E5/G6, which binds to a linear epitope in the nucleocapsid protein of hantaviruses
M. Okumura, K. Yoshimatsu, K. Araki, B. H. Lee, A. Asano, T. Agui, J. Arikawa
Archives of Virology, 149, 12, 2427, 2434, Dec. 2004
English, Scientific journal

Cell fusion activities of Hantaan virus envelope glycoproteins
Michiko Ogino, Kumiko Yoshimatsu, Hideki Ebihara, Koichi Araki, Byoung-Hee Lee, Megumi Okumura, Jiro Arikawa
Journal of Virology, 78, 19, 10776, 10782, Oct. 2004
English, Scientific journal

Cell fusion activities of Hantaan virus envelope glycoproteins
M Ogino, K Yoshimatsu, H Ebihara, K Araki, BH Lee, M Okumura, J Arikawa
JOURNAL OF VIROLOGY, 78, 19, 10776, 10782, Oct. 2004, [Peer-reviewed]
English, Scientific journal

日本におけるハンタウイルス感染の動物伝染病学的及び疫学的研究(Epizootiological and epidemiological study of hantavirus infection in Japan)　　　　　　　　　　　　　　　
Lokugamage Nandadeva, 苅和 宏明, 好井 健太朗, 舘 敦史, 安藤 秀二, 福島 博, 土屋 公幸, 岩崎 琢也, 吉松 組子, 有川 二郎, 高島 郁夫
日本獣医学会学術集会講演要旨集, 138回, 130, 130, (公社)日本獣医学会, Aug. 2004, [Peer-reviewed]
English

Amur型ハンタウイルス糖蛋白の哺乳類細胞での発現と抗原性解析　　　　　　　　　　　　　　　
舘 敦史, 苅和 宏明, Lokugamage Kumari, Lokugamage Nandadeva, 谷川 洋一, 好井 健太朗, 吉松 組子, 有川 二郎, 高島 郁夫
日本獣医学会学術集会講演要旨集, 138回, 131, 131, (公社)日本獣医学会, Aug. 2004, [Peer-reviewed]
Japanese

Age-dependent hantavirus-specific CD8(+) T-cell responses in mice infected with Hantaan virus
K Araki, K Yoshimatsu, BH Lee, M Okumura, H Kariwa, Takashima, I, J Arikawa
ARCHIVES OF VIROLOGY, 149, 7, 1373, 1382, Jul. 2004
English, Scientific journal

Genetic and antigenic characterization of the Amur virus associated with hemorrhagic fever with renal syndrome
K Lokugamage, H Kariwa, N Lokugamage, H Miyamoto, M Iwasa, T Hagiya, K Araki, A Tachi, T Mizutani, K Yoshimatsu, J Arikawa, Takashima, I
VIRUS RESEARCH, 101, 2, 127, 134, May 2004, [Peer-reviewed]
English, Scientific journal

A new model of Hantaan virus persistence in mice: the balance between HTNV infection and CD8(+) T-cell responses
K Araki, K Yoshimatsu, BH Lee, H Kariwa, Takashima, I, J Arikawa
VIROLOGY, 322, 2, 318, 327, May 2004, [Peer-reviewed]
English, Scientific journal

Comparison of virulence of various hantaviruses related to hemorrhagic fever with renal syndrome in newborn mouse model.
K Lokugamage, H Kariwa, N Lokugamage, M Iwasa, T Hagiya, K Araki, A Tachi, T Mizutani, K Yoshimatsu, J Arikawa, T Iwasaki, Takashima, I
JAPANESE JOURNAL OF VETERINARY RESEARCH, 51, 3-4, 143, 149, Feb. 2004, [Peer-reviewed]
English, Scientific journal

A new model of Hantaan virus persistence in mice: The balance between HTNV infection and CD8⁺ T-cell responses
Araki, K., Yoshimatsu, K., Lee, B.-H., Kariwa, H., Takashima, I., Arikawa, J.
Virology, 322, 2, 2004
Scientific journal

Epizootiological and epidemiological study of hantavirus infection in Japan
N Lokugamage, H Kariwa, K Lokugamage, MA Iwasa, T Hagiya, K Yoshii, A Tachi, S Ando, H Fukushima, K Tsuchiya, T Iwasaki, K Araki, K Yoshimatsu, J Arikawa, T Mizutani, K Osawa, H Sato, K Takashima
MICROBIOLOGY AND IMMUNOLOGY, 48, 11, 843, 851, 2004, [Peer-reviewed]
English, Scientific journal

Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules
BH Lee, K Yoshimatsu, A Maeda, K Ochiai, M Morimatsu, K Araki, M Ogino, S Morikawa, J Arikawa
VIRUS RESEARCH, 98, 1, 83, 91, Dec. 2003
English, Scientific journal

Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules
BH Lee, K Yoshimatsu, A Maeda, K Ochiai, M Morimatsu, K Araki, M Ogino, S Morikawa, J Arikawa
VIRUS RESEARCH, 98, 1, 83, 91, Dec. 2003, [Peer-reviewed]
English, Scientific journal

Development of an efficient method for recovery of Puumala and Puumala-related viruses by inoculation of mongolian gerbils
N Lokugamage, H Kariwa, K Lokugamage, T Hagiya, H Miyamoto, MA Iwasa, K Araki, K Yoshimatsu, J Arikawa, T Mizutani, Takashima, I
JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 11, 1189, 1194, Nov. 2003
English, Scientific journal

Development of an efficient method for recovery of Puumala and Puumala-related viruses by inoculation of mongolian gerbils
N Lokugamage, H Kariwa, K Lokugamage, T Hagiya, H Miyamoto, MA Iwasa, K Araki, K Yoshimatsu, J Arikawa, T Mizutani, Takashima, I
JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 11, 1189, 1194, Nov. 2003, [Peer-reviewed]
English, Scientific journal

Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species
BH Lee, K Yoshimatsu, K Araki, M Ogino, M Okumura, K Tsuchiya, H Kariwa, J Arikawa
ARCHIVES OF VIROLOGY, 148, 10, 1885, 1897, Oct. 2003
English, Scientific journal

Synthesis of Seoul virus RNA and structural proteins in cultured cells
H Kariwa, H Tanabe, T Mizutani, Y Kon, K Lokugamage, N Lokugamage, MA Iwasa, T Hagiya, K Araki, K Yoshimatsu, J Arikawa, Takashima, I
ARCHIVES OF VIROLOGY, 148, 9, 1671, 1685, Sep. 2003
English, Scientific journal

Serological analysis of hemorrhagic fever with renal syndrome (HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype
H Miyamoto, H Kariwa, K Araki, K Lokugamage, D Hayasaka, BZ Cui, N Lokugamage, LI Ivanov, T Mizutani, MA Iwasa, K Yoshimatsu, J Arikawa, Takashima, I
ARCHIVES OF VIROLOGY, 148, 8, 1543, 1556, Aug. 2003
English, Scientific journal

Hantavirus-specific CD8(+)-T-cell responses in newborn mice persistently infected with Hantaan virus
K Araki, K Yoshimatsu, BH Lee, H Kariwa, Takashima, I, J Arikawa
JOURNAL OF VIROLOGY, 77, 15, 8408, 8417, Aug. 2003, [Peer-reviewed]
English, Scientific journal

Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis
K Yoshii, D Hayasaka, A Goto, M Obara, K Araki, K Yoshimatsu, J Arikawa, L Ivanov, T Mizutani, H Kariwa, Takashima, I
JOURNAL OF VIROLOGICAL METHODS, 108, 2, 171, 179, Mar. 2003, [Peer-reviewed]
English, Scientific journal

Hantavirus-specific CD8⁺-T-cell responses in newborn mice persistently infected with Hantaan virus
Araki, K., Yoshimatsu, K., Lee, B.-H., Kariwa, H., Takashima, I., Arikawa, J.
Journal of Virology, 77, 15, 2003
Scientific journal

Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis
Kentarou Yoshii, Daisuke Hayasaka, Akiko Goto, Mayumi Obara, Koichi Araki, Kumiko Yoshimatsu, Jiro Arikawa, Leonoid Ivanov, Tetsuya Mizutani, Hiroaki Kariwa, Ikuo Takashima
Journal of Virological Methods, 108, 2, 171, 179, Elsevier, 2003
English, Scientific journal

Establishment of an Enzyme-Linked Immunosorbent Assay for Detection of Hantavirus Antibody of Rats Using a Recombinant of Nucleocapsid Protein Expressed in Escherichia coli.（共著）
Exp. Anim., 52(1),25-30, 2003

Use of vesicular stomatitis virus pseudotypes bearing hantaan or Seoul virus envelope proteins in a rapid and safe neutralization test
M Ogino, H Ebihara, BH Lee, K Araki, A Lundkvist, Y Kawaoka, K Yoshimatsu, J Arikawa
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 10, 1, 154, 160, Jan. 2003
English, Scientific journal

The Multimerization of Hantavirus nucleocapsid protein depends on type-specific epitopes.(共著)
Journal of Virology, J. Virol. 77(2),943-952, 2003

The intracellular association of the nucleocapsid protein (NP) of hantaan virus (HTNV) with small ubiquitin-like modifier-1 (SUMO-1) conjugating enzyme 9 (Ubc9)
A Maeda, BH Lee, K Yoshimatsu, M Saijo, Kurane, I, J Arikawa, S Morikawa
VIROLOGY, 305, 2, 288, 297, Jan. 2003
English, Scientific journal

The multimerization of hantavirus nucleocapsid protein depends on type-specific epitopes
K Yoshimatsu, BH Lee, K Araki, M Morimatsu, M Ogino, H Ebihara, J Arikawa
JOURNAL OF VIROLOGY, 77, 2, 943, 952, Jan. 2003, [Peer-reviewed]
English, Scientific journal

Use of vesicular stomatitis virus pseudotypes bearing hantaan or Seoul virus envelope proteins in a rapid and safe neutralization test
M Ogino, H Ebihara, BH Lee, K Araki, A Lundkvist, Y Kawaoka, K Yoshimatsu, J Arikawa
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 10, 1, 154, 160, Jan. 2003, [Peer-reviewed]
English, Scientific journal

The intracellular association of the nucleocapsid protein (NP) of hantaan virus (HTNV) with small ubiquitin-like modifier-1 (SUMO-1) conjugating enzyme 9 (Ubc9)
A Maeda, BH Lee, K Yoshimatsu, M Saijo, Kurane, I, J Arikawa, S Morikawa
VIROLOGY, 305, 2, 288, 297, Jan. 2003, [Peer-reviewed]
English, Scientific journal

Establishment of an enzyme-linked immunosorbent assay for detection of Hantavirus antibody of rats using a recombinant of nucleocapsid protein expressed in Escherichia coli
A Takakura, K Goto, T Itoh, K Yoshimatsu, Takashima, I, J Arikawa
EXPERIMENTAL ANIMALS, 52, 1, 25, 30, Jan. 2003, [Peer-reviewed]
English, Scientific journal

The multimerization of Hantavirus nucleocapsid protein depends on type-specific epitopes
Kumiko Yoshimatsu, Byoung-Hee Lee, Koichi Araki, Masami Morimatsu, Michiko Ogino, Hideki Ebihara, Jiro Arikawa
Journal of Virology, 77, 2, 943, 952, Jan. 2003, [Peer-reviewed]
English, Scientific journal

Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia
K Lokugamage, H Kariwa, D Hayasaka, BZ Cui, T Iwasaki, N Lokugamage, LI Ivanov, Volkov, VI, VA Demenev, R Slonova, G Kompanets, T Kushnaryova, T Kurata, K Maeda, K Araki, T Mizutani, K Yoshimatsu, J Arikawa, Takashima, I
EMERGING INFECTIOUS DISEASES, 8, 8, 768, 776, Aug. 2002, [Peer-reviewed]
English, Scientific journal

Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia
Kumari Lokugamage, Hiroaki Kariwa, Daisuke Hayasaka, Bai Zhong Cui, Takuya Iwasaki, Nandadeva Lokugamage, Leonid I. Ivanov, Vladimir I. Volkov, Vladimir A. Demenev, Raisa Slonova, Galina Kompanets, Tatyana Kushnaryova, Takeshi Kurata, Kenji Maeda, Koichi Araki, Tetsuya Mizutani, Kumiko Yoshimatsu, Jiro Arikawa, Ikuo Takashima
Emerging Infectious Diseases, 8, 8, 768, 776, Centers for Disease Control and Prevention (CDC), 2002
English, Scientific journal

Epizootiological survey of hantavirus among rodent species in Ningxia Hui Autonomous Province, China
H Kariwa, CB Zhong, K Araki, K Yoshimatsu, K Lokugamage, N Lokugamage, ME Murphy, T Mizutani, J Arikawa, H Fukushima, H Xiong, JHC Chen, Takashima, I
JAPANESE JOURNAL OF VETERINARY RESEARCH, 49, 2, 105, 114, Aug. 2001
English, Scientific journal

Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus
ME Murphy, H Kariwa, T Mizutani, H Tanabe, K Yoshimatsu, J Arikawa, Takashima, I
JOURNAL OF VETERINARY MEDICAL SCIENCE, 63, 6, 637, 645, Jun. 2001
English, Scientific journal

Truncated hantavirus nucleocapsid proteins for serotyping Hantaan, Seoul, and Dobrava hantavirus infections
K. Araki, K. Yoshimatsu, M. Ogino, H. Ebihara, A. Lundkvist, H. Kariwa, I. Takashima, J. Arikawa
Journal of Clinical Microbiology, 39, 7, 2397, 2404, 2001
English, Scientific journal

Mouse Mx2 protein inhibits hantavirus but not influenza virus replication
Jin, H.K., Yoshimatsu, K., Takada, A., Ogino, M., Asano, A., Arikawa, J., Watanabe, T.
Archives of Virology, 146, 1, 2001
Scientific journal

Pathogenicity of Hantaan virus in newborn mice: Genetic reassortant study demonstrating that a single amino acid change in glycoprotein G1 is related to virulence
H Ebihara, K Yoshimatsu, M Ogino, K Araki, Y Ami, H Kariwa, Takashima, I, DX Li, J Arikawa
JOURNAL OF VIROLOGY, 74, 19, 9245, 9255, Oct. 2000
English, Scientific journal

In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus
ME Murphy, H Kariwa, T Mizutani, K Yoshimatsu, J Arikawa, Takashima, I
ARCHIVES OF VIROLOGY, 145, 8, 1571, 1582, 2000
English, Scientific journal

Genetic diversity of hantaviruses isolated in China and characterization of novel hantaviruses isolated from Niviventer confucianus and Rattus rattus
Hua Wang, Kumiko Yoshimatsu, Hideki Ebihara, Michiko Ogino, Koichi Araki, Hiroaki Kariwa, Zhaoxiao Wang, Zhaozhuang Luo, Dexin Li, Changshou Hang, Jiro Arikawa
Virology, 278, 2, 332, 345, Academic Press Inc., 2000
English, Scientific journal

Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan
H Kariwa, K Yoshimatsu, K Araki, K Chayama, H Kumada, M Ogino, H Ebihara, ME Murphy, T Mizutani, Takashima, I, J Arikawa
MICROBIOLOGY AND IMMUNOLOGY, 44, 5, 357, 362, 2000
English, Scientific journal

26.マウスのインターフェロン誘導性抗ウイルス遺伝子Mxに関する研究
陳 喜慶, 高田 礼人, 森松 組子, 荻野 倫子, 有川 二郎, 渡辺 智正
日本疾患モデル学会記録, 16, 33, 33, 公益社団法人 日本実験動物学会, 2000
Japanese

A serosurvey of Borna disease virus infection in wild rats by a capture ELISA
K Tsujimura, T Mizutani, H Kariwa, K Yoshimatsu, M Ogino, Y Morii, H Inagaki, J Arikawa, Takashima, I
JOURNAL OF VETERINARY MEDICAL SCIENCE, 61, 2, 113, 117, Feb. 1999
English, Scientific journal

Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia
H Kariwa, K Yoshimatsu, J Sawabe, E Yokota, J Arikawa, Takashima, I, H Fukushima, A Lundkvist, FN Shubin, LM Isachkova, RA Slonova, GN Leonova, N Hashimoto
VIRUS RESEARCH, 59, 2, 219, 228, Feb. 1999
English, Scientific journal

A Serosurvey of Borna Disease Virus Infection in Wild Rats by a Capture ELISA
Koji Tsujimura, Tetsuya Mizutani, Hiroaki Kariwa, Kumiko Yoshimatsu, Michiko Ogino, Yuko Morii, Hisae Inagaki, Jiro Arikawa, Ikuo Takashima
Journal of Veterinary Medical Science, 61, 2, 113, 117, Feb. 1999, [Peer-reviewed]
English, Scientific journal

Hantavirus infection of SD rats reared in domestic laboratory animal facilities.（共著）　　　　　　　　　　　　　　　
Korean Journal of the laboratory Animal Science, 15(1),49-52, 1999

N-acetylgalactosamine (GalNAc)-specific lectins mediate enhancement of Hantaan virus infection
M Ogino, K Yoshimatsu, H Ebihara, J Arikawa
ARCHIVES OF VIROLOGY, 144, 9, 1765, 1777, 1999
English, Scientific journal

Antigenic characterization of Hantaan and Seoul virus nucleocapsid proteins expressed by recombinant baculovirus: Application of a truncated protein, lacking an antigenic region common to the two viruses, as a serotyping antigen
M Morii, K Yoshimatsu, J Arikawa, GZ Zhou, H Kariwa, Takashima, I
JOURNAL OF CLINICAL MICROBIOLOGY, 36, 9, 2514, 2521, Sep. 1998
English, Scientific journal

Evaluation of serological diagnosis of Borna disease virus infection using recombinant proteins in experimentally infected rats
M Ogino, K Yoshimatsu, K Tsujimura, T Mizutani, J Arikawa, Takashima, I
JOURNAL OF VETERINARY MEDICAL SCIENCE, 60, 4, 531, 534, Apr. 1998
English, Scientific journal

Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine
YC Yoo, K Yoshimatsu, Y Koike, R Hatsuse, K Yamanishi, O Tanishita, J Arikawa, Azuma, I
VACCINE, 16, 2-3, 216, 224, Jan. 1998
English, Scientific journal

Characterization of neutralizing monoclonal antibody escape mutants of Hantaan virus 76118
M Kikuchi, K Yoshimatsu, J Arikawa, R Yoshida, YC Yoo, Y Isegawa, K Yamanishi, S Tono-oka, Azuma, I
ARCHIVES OF VIROLOGY, 143, 1, 73, 83, 1998
English, Scientific journal

Urine-associated horizontal transmission of Seoul virus among rats
H Kariwa, M Fujiki, K Yoshimatsu, J Arikawa, Takashima, I, N Hashimoto
ARCHIVES OF VIROLOGY, 143, 1, 15, 24, 1998
English, Scientific journal

Urine-associated horizontal transmission of Seoul virus among rats
H Kariwa, M Fujiki, K Yoshimatsu, J Arikawa, Takashima, I, N Hashimoto
ARCHIVES OF VIROLOGY, 143, 2, 365, 374, 1998, [Peer-reviewed]
English, Scientific journal

Hantavirus infection in SCID mice
K Yoshimatsu, J Arikawa, S Ohbora, C Itakura
JOURNAL OF VETERINARY MEDICAL SCIENCE, 59, 10, 863, 868, Oct. 1997
English, Scientific journal

A case of tick-borne encephalitis in Japan and isolation of the virus
Takashima, I, K Morita, M Chiba, D Hayasaka, T Sato, C Takezawa, A Igarashi, H Kariwa, K Yoshimatsu, J Arikawa, N Hashimoto
JOURNAL OF CLINICAL MICROBIOLOGY, 35, 8, 1943, 1947, Aug. 1997
English, Scientific journal

Protective effect of mucosal administration of recombinant human macrophage colony stimulating factor (rhM-CSF) on mucosal infection of Sendai virus in mice
K Matsuzawa, YC Yoo, A Fukushima, K Yoshimatsu, J Arikawa, Azuma, I
VACCINE, 15, 1, 85, 89, Jan. 1997
English, Scientific journal

Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus
A Fukushima, YC Yoo, K Yoshimatsu, K Matsuzawa, M Tamura, S Tonooka, K Taniguchi, S Urasawa, J Arikawa, Azuma, I
VACCINE, 14, 6, 485, 491, Apr. 1996
English, Scientific journal

Characterization of the nucleocapsid protein of Hantaan virus strain 76-118 using monoclonal antibodies
K Yoshimatsu, J Arikawa, M Tamura, R Yoshida, A Lundkvist, B Niklasson, H Kariwa, Azuma, I
JOURNAL OF GENERAL VIROLOGY, 77, 695, 704, Apr. 1996
English, Scientific journal

Modes of Seoul virus infections: Persistency in newborn rats and transiency in adult rats
H Kariwa, M Kimura, S Yoshizumi, J Arikawa, K Yoshimatsu, Takashima, I, N Hashimoto
ARCHIVES OF VIROLOGY, 141, 12, 2327, 2338, 1996
English, Scientific journal

Western blotting using recombinant hantaan virus nucleocapsid protein expressed in silkworm as a serological confirmation of hantavirus infection in human sera
K Yoshimatsu, J Arikawa, H Li, H Kariwa, N Hashimoto
JOURNAL OF VETERINARY MEDICAL SCIENCE, 58, 1, 71, 74, Jan. 1996
English, Scientific journal

Production of recombinant hantavirus nucleocapsid protein expressed in silkworm larvae and its use as a diagnostic antigen in detecting antibodies in serum from infected rats
K Yoshimatsu, J Arikawa, R Yoshida, H Li, YC Yoo, H Kariwa
LABORATORY ANIMAL SCIENCE, 45, 6, 641, 646, Dec. 1995
English, Scientific journal

EFFECT OF MDP-LYS(L18), A DERIVATIVE OF MDP, ON ENHANCING HOST-RESISTANCE AGAINST HANTAAN VIRUS-INFECTION IN NEWBORN MICE
YC YOO, K YOSHIMATSU, R HATSUSE, M TAMURA, R YOSHIDA, S TONOOKA, J ARIKAWA, AZUMA, I
VACCINE, 13, 14, 1300, 1305, Oct. 1995
English, Scientific journal

EVIDENCE FOR THE EXISTENCE OF PUUMULA-RELATED VIRUS AMONG CLETHRIONOMYS RUFOCANUS IN HOKKAIDO, JAPAN
H KARIWA, S YOSHIZUMI, J ARIKAWA, K YOSHIMATSU, K TAKAHASHI, TAKASHIMA, I, N HASHIMOTO
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 53, 3, 222, 227, Sep. 1995
English, Scientific journal

EFFECTS OF MURAMYL DIPEPTIDE DERIVATIVES AS ADJUVANTS ON THE INDUCTION OF ANTIBODY-RESPONSE TO RECOMBINANT HEPATITIS-B SURFACE-ANTIGEN
M TAMURA, YC YOO, K YOSHIMATSU, R YOSHIDA, T OKA, K OHKUMA, J ARIKAWA, AZUMA, I
VACCINE, 13, 1, 77, 82, Jan. 1995
English, Scientific journal

CHARACTERIZATION OF THE MODE OF HANTAAN VIRUS-INFECTION IN ADULT MICE USING A NESTED REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION - TRANSIENT VIRUS-REPLICATION IN ADULT MICE
H KARIWA, M KAMIMURA, J ARIKAWA, K YOSHIMATSU, TAKASHIMA, I, N HASHIMOTO
MICROBIOLOGY AND IMMUNOLOGY, 39, 1, 35, 41, 1995
English, Scientific journal

EFFECT OF THE SYNTHETIC LIPID A-RELATED COMPOUND, DT-5461, ON RESISTANCE TO SENDAI VIRUS-INFECTION IN MICE
R YOSHIDA, K SATO, YC YOO, K YOSHIMATSU, M TAMURA, C ISHIHARA, J ARIKAWA, AZUMA, I
IMMUNOPHARMACOLOGY, 28, 2, 153, 161, Sep. 1994
English, Scientific journal

PROTECTIVE ACTIVITY OF MDP-LYS(L18) ON HANTAVIRUS INFECTION IN NEWBORN MICE AND POTENTIATION OF ANTIGENICITY BY B30-MDP AND MDP-LYS(L18) OF INACTIVATED HANTAVIRUS STRAIN B-1 VACCINE AND RECOMBINANT HEPATITIS-B VIRUS SURFACE-ANTIGEN
AZUMA, I, YC YOO, M TAMURA, R YOSHIDA, K YOSHIMATSU, J ARIKAWA, K YAMANISHI
IMMUNOTHERAPY OF INFECTIONS, 15, 191, 203, 1994, [Peer-reviewed]
English, International conference proceedings

APPLICATION OF A RECOMBINANT BACULOVIRUS EXPRESSING HANTAVIRUS NUCLEOCAPSID PROTEIN AS A DIAGNOSTIC ANTIGEN IN IFA TEST - CROSS-REACTIVITIES AMONG 3 SEROTYPES OF HANTAVIRUS WHICH CAUSES HEMORRHAGIC-FEVER RENAL SYNDROME (HFRS)
K YOSHIMATSU, J ARIKAWA, H KARIWA
JOURNAL OF VETERINARY MEDICAL SCIENCE, 55, 6, 1047, 1050, Dec. 1993
English

POSTNATAL CHANGE OF PIG INTESTINAL GANGLIOSIDE BOUND BY ESCHERICHIA-COLI WITH K99 FIMBRIAE
Y YUYAMA, K YOSHIMATSU, E ONO, M SAITO, M NAIKI
JOURNAL OF BIOCHEMISTRY, 113, 4, 488, 492, Apr. 1993
English, Scientific journal

ANTIVIRAL ACTIVITY OF SULFATED CHITIN DERIVATIVES AGAINST FRIEND MURINE LEUKEMIA AND HERPES-SIMPLEX TYPE-1 VIRUSES
C ISHIHARA, K YOSHIMATSU, M TSUJI, J ARIKAWA, SAIKI, I, S TOKURA, AZUMA, I
VACCINE, 11, 6, 670, 674, Apr. 1993
English, Scientific journal

PROTECTIVE IMMUNITY OF HANTAAN VIRUS NUCLEOCAPSID AND ENVELOPE PROTEIN STUDIED USING BACULOVIRUS-EXPRESSED PROTEINS
K YOSHIMATSU, YC YOO, R YOSHIDA, C ISHIHARA, AZUMA, I, J ARIKAWA
ARCHIVES OF VIROLOGY, 130, 3-4, 365, 376, 1993
English, Scientific journal

COMPARISON OF VIRULENCE BETWEEN SEOUL VIRUS-STRAIN SR-11 AND HANTAAN VIRUS-STRAIN 76-118 OF HANTAVIRUSES IN NEWBORN MICE
YC YOO, K YOSHIMATSU, R YOSHIDA, M TAMURA, AZUMA, I, J ARIKAWA
MICROBIOLOGY AND IMMUNOLOGY, 37, 7, 557, 562, 1993
English, Scientific journal

EFFECT OF NEUTRALIZING MONOCLONAL-ANTIBODIES ON HANTAAN VIRUS-INFECTION OF THE MACROPHAGE P388D1-CELL LINE
JS YAO, J ARIKAWA, H KARIWA, K YOSHIMATSU, TAKASHIMA, I, N HASHIMOTO
JAPANESE JOURNAL OF VETERINARY RESEARCH, 40, 2-3, 87, 97, Sep. 1992, [Peer-reviewed]
English, Scientific journal

ISOLATION OF C-REACTIVE PROTEIN FROM CAT SERUM
A WATANABE, M MORIMATSU, K YOSHIMATSU, S YAMAMOTO, A TERAO, K TSUKAZAKI, M SAITO, M NAIKI
JOURNAL OF SMALL ANIMAL PRACTICE, 33, 2, 71, 77, Feb. 1992, [Peer-reviewed]
English, Scientific journal

Isolation and characterization of conglutinin as an influenza A virus inhibitor
Wakamiya, N., Okuno, Y., Sasao, F., Ueda, S., Yoshimatsu, K., Naiki, M., Kurimura, T.
Biochemical and Biophysical Research Communications, 187, 3, 1992
Scientific journal

STIMULATION OF HOST-DEFENSE MECHANISM WITH SYNTHETIC ADJUVANTS AND RECOMBINANT CYTOKINES AGAINST VIRAL-INFECTION IN MICE
AZUMA, I, C ISHIHARA, J IIDA, YC YOO, K YOSHIMATSU, J ARIKAWA
MICROBIAL INFECTIONS, 319, 253, 263, 1992, [Peer-reviewed]
English, International conference proceedings

ANTIBODY-DEPENDENT ENHANCEMENT OF HANTAVIRUS INFECTION IN MACROPHAGE CELL-LINES
JS YAO, H KARIWA, TAKASHIMA, I, K YOSHIMATSU, J ARIKAWA, N HASHIMOTO
ARCHIVES OF VIROLOGY, 122, 1-2, 107, 118, 1992, [Peer-reviewed]
English, Scientific journal

PROTECTIVE ROLE OF ANTIGENIC SITES ON THE ENVELOPE PROTEIN OF HANTAAN VIRUS DEFINED BY MONOCLONAL-ANTIBODIES
J ARIKAWA, JS YAO, K YOSHIMATSU, TAKASHIMA, I, N HASHIMOTO
ARCHIVES OF VIROLOGY, 126, 1-4, 271, 281, 1992, [Peer-reviewed]
English, Scientific journal

ELEVATION OF BOVINE SERUM C-REACTIVE PROTEIN AND SERUM AMYLOID-P COMPONENT LEVELS BY LACTATION
M MORIMATSU, A WATANABE, K YOSHIMATSU, T FUJINAGA, M OKUBO, M NAIKI
JOURNAL OF DAIRY RESEARCH, 58, 3, 257, 261, Aug. 1991, [Peer-reviewed]
English, Scientific journal

ISOLATION AND CHARACTERIZATION OF C-REACTIVE PROTEIN AND SERUM AMYLOID-P COMPONENT FROM BOVINE SERUM
M MORIMATSU, H SAKAI, K YOSHIMATSU, O MINOWA, S YAMAMOTO, K YATOMI, T FUJINAGA, M NAIKI
JAPANESE JOURNAL OF VETERINARY SCIENCE, 51, 4, 723, 732, Aug. 1989, [Peer-reviewed], [International Magazine]
English, Scientific journal

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

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

Reply to comments by Yih et al. (Exposure to hantavirus is a risk factor associated with kidney diseases in Sri Lanka: A cross-sectional study)
Yomani D. Sarathkumara, Chandika D. Gamage, Sithumini Lokupathirage, Devinda S. Muthusinghe, Nishantha Nanayakkara, Lishanthe Gunarathne, Kenta Shimizu, Yoshimi Tsuda, Jiro Arikawa, Kumiko Yoshimatsu, Viruses, 11, 12, 11 Dec. 2019
MDPI AG, English, Report scientific journal

東アジアの小型哺乳動物から分離されたレプトスピラの反復配列多型解析法による分子型別
小泉信夫, 泉谷秀昌, 慕蓉蓉, 岡野祥, 中島千絵, 鈴木定彦, 谷川力, 小松謙之, 吉松組子, 武藤(水谷)麻紀, 武藤(水谷)麻紀, 大西真, レプトスピラ・シンポジウム, 53rd, 2016

イムノクロマトグラフィー法によるハンタウイルスの迅速診断法の開発　　　　　　　　　　　　　　　
小山 芽以, 吉松 組子, 好井 健太朗, 有川 二郎, 苅和 宏明, 日本獣医学会学術集会講演要旨集, 158回, 373, 373, Aug. 2015
(公社)日本獣医学会, Japanese

Hantavirus Pulmonary Syndrome
吉松 組子, 有川 二郎, 医学のあゆみ, 253, 1, 63, 67, 04 Apr. 2015
医歯薬出版, Japanese

マウスを用いた腎症候性出血熱の疾患モデルの開発
清水健太, 吉松組子, 駒貴明, 有川二郎, 日本実験動物学会総会講演要旨集, 61st, 2014

【人と動物の共通感染症最前線10】 日本のげっ歯類におけるハンタウイルス感染の血清疫学調査とエゾヤチネズミが保有するHokkaidoウイルスの分離
苅和 宏明, 尾崎 由佳, 真田 崇弘, 池中 良徳, 石塚 真由美, 坪田 敏男, 好井 健太朗, 吉松 組子, 有川 二郎, 高島 郁夫, 獣医畜産新報, 66, 4, 262, 264, Apr. 2013
文永堂出版(株), Japanese

新世界ハンタウイルス感染症の血清型鑑別診断のための組換え核蛋白を用いた新規ELISA法の開発
駒 貴明, 吉松 組子, 垂石 みどり, 宮下 大輔, 遠藤 理香, 清水 健太, 安田 俊平, 天田 貴子, 瀬戸 隆弘, 村田 亮, 吉田 喜香, 苅和 宏明, 高島 郁夫, 有川 二郎, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 88, 1, 35, 35, 01 Jan. 2013
Japanese

Environmental enrichment after the occurrence of wet bedding and the appearance of abnormal fur in mice is effective for solving those problems
TOSA Noriko, YOSHIMATSU Kumiko, ARIKAWA Jiro, 実験動物と環境 = Laboratory animal and environment, 20, 1, 1, 8, 01 Apr. 2012
English

腎症候性出血熱の動物モデルの開発
清水健太, 吉松組子, 駒貴明, 伊勢川裕二, 安田俊平, 天田貴子, 五十棲理恵, 有川二郎, 日本獣医学会学術集会講演要旨集, 153rd, 2012

ベトナムのラットおよびヒトにおけるラットE型肝炎ウイルスの感染状況の調査
清水健太, 李天成, 安田俊平, 吉松組子, 駒貴明, 長谷部太, 山城哲, HOA Nguyen Thuy, MAI Le Thi Quynh, 有川二郎, 日本獣医学会学術集会講演要旨集, 154th, 2012

肺水腫を呈すハンタウイルス感染SCIDマウスに於ける好中球の役割
駒貴明, 永田典代, 吉松組子, 佐藤由子, 清水健太, 天田貴子, 西尾佐奈恵, 長谷川秀樹, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012

イムノクロマト法による抗ハンタウイルス抗体の迅速抗体検出法の開発
天田貴子, 吉松組子, 安田俊平, 清水健太, 駒貴明, 林元展人, 高倉彰, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012

イムノクロマト法による抗ハンタウイルス抗体の迅速抗体検出法の開発
天田貴子, 吉松組子, 安田俊平, 駒貴明, 清水健太, 五十棲理恵, 林元展人, 高倉彰, 有川二郎, 日本獣医学会学術集会講演要旨集, 153rd, 2012

腎症候性出血熱の動物モデルの開発と病態発現機構の解析
清水健太, 吉松組子, 駒貴明, 天田貴子, 西尾佐奈恵, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 2012

イムノクロマト法によるラットとヒト血清のハンタウイルス抗体迅速検出法の開発
有川二郎, 天田貴子, 林元展人, 吉松組子, 安田俊平, 清水健太, 駒貴明, 五十棲理恵, 高倉彰, 日本実験動物学会総会講演要旨集, 59th, 2012

エゾヤチネズミ(Myodes rufocanus bedfordiae)の腎臓由来細胞株の樹立とHokkaidoウイルス分離への応用
真田崇弘, 瀬戸隆弘, 尾崎由佳, NGONDA Saasa, 吉松組子, 有川二郎, 好井健太朗, 苅和宏明, 日本ウイルス学会北海道支部夏季シンポジウム講演抄録, 46th, 2012

ハンタウイルス糖蛋白質の細胞内輸送に関与するウイルス蛋白質とその機能領域
清水健太, 吉松組子, 駒貴明, 安田俊平, 有川二郎, 日本獣医学会学術集会講演要旨集, 152nd, 2011

免疫不全マウスを用いたハンタウイルス感染症病態モデルの検討
駒貴明, 吉松組子, 永田典代, 清水健太, 安田俊平, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 2010

ハンタウイルス持続感染メカニズム解明のための実験感染ラットを用いた細胞性免疫測定系の確立
安田俊平, 吉松組子, 遠藤理香, 清水健太, 駒貴明, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 2010

ハンタウイルスGlycoproteinの細胞内動態に及ぼすNucleocapsid proteinの影響
清水健太, 吉松組子, 駒貴明, 安田俊平, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 2010

ハンタウイルスNucleocapsid proteinはGlycoprotein Gcのシスゴルジへの局在を促進する
清水健太, 吉松組子, 駒貴明, 遠藤理香, 安田俊平, ERDENESAIKHAN Tegshduuren, 有川二郎, 日本獣医学会学術集会講演要旨集, 150th, 2010

メキシコの野生げっ歯類が保有するハンタウイルスの抗原性解析
吉田喜香, 苅和宏明, 真田崇弘, NGONDA Saasa, 瀬戸隆弘, 吉松組子, 有川二郎, 好井健太朗, 高島郁夫, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 2010

インドネシアのげっ歯類におけるハンタウイルス感染症の疫学
清水健太, イブラヒムイマヌリサ, 吉松組子, 遠藤理香, 安田俊平, 駒貴明, エルテネサイハンテグシドーレン, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 2009

トガリネズミ目(旧食虫目)由来ハンタウイルスThottapalayamウイルス(TPMV)核蛋白の単クローン抗体を用いた抗原領域の解析
エルテネサイハンテグシドーレン, 清水健太, 吉松組子, 遠藤理香, 駒貴明, 安田俊平, 有川二郎, 石原智明, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 2009

ハンタウイルス自然感染ラットと実験感染ラットにおける病態の比較
安田俊平, 吉松組子, 遠藤理香, 清水健太, 駒貴明, TEGSHDUUREN Erdenesaikhan, 垂石みどり, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 2009

汎用PCRプライマーを用いたハンタウイルス遺伝子検出スクリーニング法の確立
遠藤理香, 吉松組子, 駒貴明, 清水健太, 安田俊平, TEGSHDUUREN Erdenesaihan, 垂石みどり, 海老原秀喜, 宮下大輔, 瀬戸隆弘, HERNANDEZ Cornelio S., ALMARAZ Maria L.R., RAMOS Celso, 苅和宏明, 高島郁夫, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 2009

新世界ハンタウイルス感染の血清型鑑別ELISA法の確立
駒貴明, 吉松組子, 垂石みどり, 遠藤理香, 清水健太, 安田俊平, エルテネサイハンテグシドーレン, 海老原秀喜, HERNANDEZ Cornelio S., ALMARAZ Maria L.R., RAMOS Celso, 宮下大輔, 瀬戸隆弘, 苅和宏明, 高島郁夫, ENRIA Delia, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 57th, 2009

新世界ハンタウイルス感染の血清型鑑別ELISA法の確立
駒貴明, 吉松組子, 垂石みどり, 遠藤理香, 清水健太, 安田俊平, テグシドーレン エルデネサイハン, 海老原秀喜, HERNANDEZ Cornelio S., ALMARAZ Maria L.R., RAMOS Celso, 宮下大輔, 瀬戸隆弘, 苅和宏明, 高島郁夫, ENRIA Delia, 有川二郎, 日本ウイルス学会北海道支部夏季シンポジウム講演抄録, 43rd, 2009

複数のハンタウイルス血清型に対応可能な診断法の開発
真田崇弘, 苅和宏明, 瀬戸隆弘, 谷川洋一, 宮下大輔, 吉松組子, 有川二郎, 好井健太朗, 高島郁夫, 日本ウイルス学会北海道支部夏季シンポジウム講演抄録, 43rd, 2009

Evidence of Hantavirus Infection Among Rodents in South India
S. Chandy, K. Yoshimatsu, R. G. Ulrich, M. Schlegel, D. J. Prakash, V. Balraj, P. Abraham, J. Arikawa, G. Sridharan, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 12, E131, E131, Dec. 2008
English, Summary international conference

新世界ハンタウイルス感染の血清型鑑別診断法の確立
駒貴明, 吉松組子, 垂石みどり, 遠藤理香, 海老原秀喜, 有川二郎, 日本ウイルス学会学術集会プログラム・抄録集, 56th, 2008

ロシアのボルガ川流域におけるハンタウイルス感染症の疫学的研究
瀬戸隆弘, 苅和宏明, 谷川洋一, 吉松組子, 中村一郎, 宮下大輔, 中内美名, 好井健太朗, 有川二郎, 高島郁夫, 日本ウイルス学会学術集会プログラム・抄録集, 55th, 2007

メキシコの野生げっ歯類におけるハンタウイルス感染症の疫学調査
宮下大輔, 苅和宏明, 瀬戸隆弘, 好井健太郎, 吉松組子, 有川二郎, 高島郁夫, 日本ウイルス学会学術集会プログラム・抄録集, 55th, 2007

東アジアの人とげっ歯類のおけるハンタウイルス感染の疫学的研究 (特集 人と動物の共通感染症最前線(2))
有川 二郎, 吉松 組子, Kumperasart Sanit, 獣医畜産新報, 58, 4, 326, 328, Apr. 2005
文永堂出版, Japanese

Nucleocapsid protein of cell culture-adapted Seoul virus strain 80-39: Analysis of its encoding sequence, expression in yeast and immuno-reactivity
Jonas Schmidt, Burkhard Jandrig, Boris Klempa, Kumiko Yoshimatsu, Jiro Arikawa, Helga Meisel, Matthias Niedrig, Christian Pitra, Detlev H. Krüger, Rainer Ulrich, Virus Genes, 30, 1, 37, 48, Jan. 2005
English

Epitope analysis of monoclonal antibody E5/G6, which binds to a linear epitope in the nucleocapsid protein of hantaviruses
M Okumura, K Yoshimatsu, K Araki, BH Lee, A Asano, T Agui, J Arikawa, ARCHIVES OF VIROLOGY, 149, 12, 2427, 2434, Dec. 2004
English

Cell fusion activities of Hantaan virus envelope glycoproteins
Michiko Ogino, Kumiko Yoshimatsu, Hideki Ebihara, Koichi Araki, Byoung-Hee Lee, Megumi Okumura, Jiro Arikawa, Journal of Virology, 78, 19, 10776, 10782, Oct. 2004
English

Age-dependent hantavirus-specific CD8(+) T-cell responses in mice infected with Hantaan virus
K Araki, K Yoshimatsu, BH Lee, M Okumura, H Kariwa, Takashima, I, J Arikawa, ARCHIVES OF VIROLOGY, 149, 7, 1373, 1382, Jul. 2004
English

Antigenic and genetic diversity of hantaviruses isolated in far eastern Asian region
J Arikawa, K Yoshimatsu, H Wang, H Kariwa, K Lokugamage, N Lokugamage, Takashima, I, JOURNAL OF CLINICAL VIROLOGY, 28, S28, S28, Dec. 2003
English, Summary international conference

Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules
BH Lee, K Yoshimatsu, A Maeda, K Ochiai, M Morimatsu, K Araki, M Ogino, S Morikawa, J Arikawa, VIRUS RESEARCH, 98, 1, 83, 91, Dec. 2003
English

Development of an efficient method for recovery of Puumala and Puumala-related viruses by inoculation of mongolian gerbils
N Lokugamage, H Kariwa, K Lokugamage, T Hagiya, H Miyamoto, MA Iwasa, K Araki, K Yoshimatsu, J Arikawa, T Mizutani, Takashima, I, JOURNAL OF VETERINARY MEDICAL SCIENCE, 65, 11, 1189, 1194, Nov. 2003
English

Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species
BH Lee, K Yoshimatsu, K Araki, M Ogino, M Okumura, K Tsuchiya, H Kariwa, J Arikawa, ARCHIVES OF VIROLOGY, 148, 10, 1885, 1897, Oct. 2003
English

Synthesis of Seoul virus RNA and structural proteins in cultured cells
H Kariwa, H Tanabe, T Mizutani, Y Kon, K Lokugamage, N Lokugamage, MA Iwasa, T Hagiya, K Araki, K Yoshimatsu, J Arikawa, Takashima, I, ARCHIVES OF VIROLOGY, 148, 9, 1671, 1685, Sep. 2003
English

Serological analysis of hemorrhagic fever with renal syndrome (HFRS) patients in Far Eastern Russia and identification of the causative hantavirus genotype
H Miyamoto, H Kariwa, K Araki, K Lokugamage, D Hayasaka, BZ Cui, N Lokugamage, LI Ivanov, T Mizutani, MA Iwasa, K Yoshimatsu, J Arikawa, Takashima, I, ARCHIVES OF VIROLOGY, 148, 8, 1543, 1556, Aug. 2003
English

Hantavirus-specific CD8(+)-T-cell responses in newborn mice persistently infected with Hantaan virus
K Araki, K Yoshimatsu, BH Lee, H Kariwa, Takashima, I, J Arikawa, JOURNAL OF VIROLOGY, 77, 15, 8408, 8417, Aug. 2003
English

Enzyme-linked immunosorbent assay using recombinant antigens expressed in mammalian cells for serodiagnosis of tick-borne encephalitis
K Yoshii, D Hayasaka, A Goto, M Obara, K Araki, K Yoshimatsu, J Arikawa, L Ivanov, T Mizutani, H Kariwa, Takashima, I, JOURNAL OF VIROLOGICAL METHODS, 108, 2, 171, 179, Mar. 2003
English

Establishment of an enzyme-linked immunosorbent assay for detection of Hantavirus antibody of rats using a recombinant of nucleocapsid protein expressed in Escherichia coli
A Takakura, K Goto, T Itoh, K Yoshimatsu, Takashima, I, J Arikawa, EXPERIMENTAL ANIMALS, 52, 1, 25, 30, Jan. 2003
English

Use of vesicular stomatitis virus pseudotypes bearing hantaan or Seoul virus envelope proteins in a rapid and safe neutralization test
M Ogino, H Ebihara, BH Lee, K Araki, A Lundkvist, Y Kawaoka, K Yoshimatsu, J Arikawa, CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 10, 1, 154, 160, Jan. 2003
English

The multimerization of Hantavirus nucleocapsid protein depends on type-specific epitopes
Kumiko Yoshimatsu, Byoung-Hee Lee, Koichi Araki, Masami Morimatsu, Michiko Ogino, Hideki Ebihara, Jiro Arikawa, Journal of Virology, 77, 2, 943, 952, Jan. 2003
English

Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia
K Lokugamage, H Kariwa, D Hayasaka, BZ Cui, T Iwasaki, N Lokugamage, LI Ivanov, Volkov, VI, VA Demenev, R Slonova, G Kompanets, T Kushnaryova, T Kurata, K Maeda, K Araki, T Mizutani, K Yoshimatsu, J Arikawa, Takashima, I, EMERGING INFECTIOUS DISEASES, 8, 8, 768, 776, Aug. 2002
English

Epizootiological survey of hantavirus among rodent species in Ningxia Hui Autonomous Province, China
H Kariwa, CB Zhong, K Araki, K Yoshimatsu, K Lokugamage, N Lokugamage, ME Murphy, T Mizutani, J Arikawa, H Fukushima, H Xiong, JHC Chen, Takashima, I, JAPANESE JOURNAL OF VETERINARY RESEARCH, 49, 2, 105, 114, Aug. 2001
English

Truncated hantavirus nucleocapsid proteins for serotyping Hantaan, Seoul, and Dobrava hantavirus infections
K Araki, K Yoshimatsu, M Ogino, H Ebihara, A Lundkvist, H Kariwa, Takashima, I, J Arikawa, JOURNAL OF CLINICAL MICROBIOLOGY, 39, 7, 2397, 2404, Jul. 2001
English

Characterization of in vitro and in vivo antiviral activity of lactoferrin and ribavirin upon hantavirus
ME Murphy, H Kariwa, T Mizutani, H Tanabe, K Yoshimatsu, J Arikawa, Takashima, I, JOURNAL OF VETERINARY MEDICAL SCIENCE, 63, 6, 637, 645, Jun. 2001
English

Epidemiology and epizootiology of hantavirus infection in Japan
J Arikawa, K Yoshimatsu, H Kariwa, JAPANESE JOURNAL OF INFECTIOUS DISEASES, 54, 3, 95, 102, Jun. 2001
English, Book review

Mouse Mx2 protein inhibits hantavirus but not influenza virus replication
HK Jin, K Yoshimatsu, A Takada, M Ogino, A Asano, J Arikawa, T Watanabe, ARCHIVES OF VIROLOGY, 146, 1, 41, 49, 2001
English

Genetic diversity of hantaviruses isolated in China and characterization of novel hantaviruses isolated from Niviventer confucianus and Rattus rattus
H Wang, K Yoshimatsu, H Ebihara, M Ogino, K Araki, H Kariwa, ZX Wang, ZZ Luo, DX Li, CS Hang, J Arikawa, VIROLOGY, 278, 2, 332, 345, Dec. 2000
English

Pathogenicity of Hantaan virus in newborn mice: Genetic reassortant study demonstrating that a single amino acid change in glycoprotein G1 is related to virulence
H Ebihara, K Yoshimatsu, M Ogino, K Araki, Y Ami, H Kariwa, Takashima, I, DX Li, J Arikawa, JOURNAL OF VIROLOGY, 74, 19, 9245, 9255, Oct. 2000
English

In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus
ME Murphy, H Kariwa, T Mizutani, K Yoshimatsu, J Arikawa, Takashima, I, ARCHIVES OF VIROLOGY, 145, 8, 1571, 1582, 2000
English

Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan
H Kariwa, K Yoshimatsu, K Araki, K Chayama, H Kumada, M Ogino, H Ebihara, ME Murphy, T Mizutani, Takashima, I, J Arikawa, MICROBIOLOGY AND IMMUNOLOGY, 44, 5, 357, 362, 2000
English

A serosurvey of Borna disease virus infection in wild rats by a capture ELISA
K Tsujimura, T Mizutani, H Kariwa, K Yoshimatsu, M Ogino, Y Morii, H Inagaki, J Arikawa, Takashima, I, JOURNAL OF VETERINARY MEDICAL SCIENCE, 61, 2, 113, 117, Feb. 1999
English

Genetic diversities of hantaviruses among rodents in Hokkaido, Japan and Far East Russia
H Kariwa, K Yoshimatsu, J Sawabe, E Yokota, J Arikawa, Takashima, I, H Fukushima, A Lundkvist, FN Shubin, LM Isachkova, RA Slonova, GN Leonova, N Hashimoto, VIRUS RESEARCH, 59, 2, 219, 228, Feb. 1999
English

N-acetylgalactosamine (GalNAc)-specific lectins mediate enhancement of Hantaan virus infection
M Ogino, K Yoshimatsu, H Ebihara, J Arikawa, ARCHIVES OF VIROLOGY, 144, 9, 1765, 1777, 1999
English

Evaluation of serological diagnosis of Borna disease virus infection using recombinant proteins in experimentally infected rats
M Ogino, K Yoshimatsu, K Tsujimura, T Mizutani, J Arikawa, Takashima, I, JOURNAL OF VETERINARY MEDICAL SCIENCE, 60, 4, 531, 534, Apr. 1998
English

Antigenic characterization of Hantaan and Seoul virus nucleocapsid proteins expressed by recombinant baculovirus. application of a truncated protein, lacking an antigenic region common to the two virus."jointly worked"　　　　　　　　　　　　　　　
Journal of clinical Microbiology, 36(9 ),2514-2521, 1998

Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine
YC Yoo, K Yoshimatsu, Y Koike, R Hatsuse, K Yamanishi, O Tanishita, J Arikawa, Azuma, I, VACCINE, 16, 2-3, 216, 224, Jan. 1998
English

Characterization of neutralizing monoclonal antibody escape mutants of Hantaan virus 76118
M Kikuchi, K Yoshimatsu, J Arikawa, R Yoshida, YC Yoo, Y Isegawa, K Yamanishi, S Tono-oka, Azuma, I, ARCHIVES OF VIROLOGY, 143, 1, 73, 83, 1998
English

Urine-associated horizontal transmission of Seoul virus among rats
H Kariwa, M Fujiki, K Yoshimatsu, J Arikawa, Takashima, I, N Hashimoto, ARCHIVES OF VIROLOGY, 143, 1, 15, 24, 1998
English

Hantavirus infection in SCID mice
K Yoshimatsu, J Arikawa, S Ohbora, C Itakura, JOURNAL OF VETERINARY MEDICAL SCIENCE, 59, 10, 863, 868, Oct. 1997
English

A case of tick-borne encephalitis in Japan and isolation of the virus
Takashima, I, K Morita, M Chiba, D Hayasaka, T Sato, C Takezawa, A Igarashi, H Kariwa, K Yoshimatsu, J Arikawa, N Hashimoto, JOURNAL OF CLINICAL MICROBIOLOGY, 35, 8, 1943, 1947, Aug. 1997
English

Protective effect of mucosal administration of recombinant human macrophage colony-stimulating factor (rhM-CSF) on mucosal infection of Sendai virus in mice.
Kaori Matsuzawa, Yung Choon Yoo, Akihisa Fukushima, Kumiko Yoshimatsu, Jiro Arikawa, Ichiro Azuma., Collected papers from the Institute of Immunological Science Hokkaido University, 20, 171, 175, 1997
Hokkaido University, English

Protective effect of mucosal administration of recombinant human macrophage colony stimulating factor (rhM-CSF) on mucosal infection of Sendai virus in mice
K Matsuzawa, YC Yoo, A Fukushima, K Yoshimatsu, J Arikawa, Azuma, I, VACCINE, 15, 1, 85, 89, Jan. 1997
English

Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus
A Fukushima, YC Yoo, K Yoshimatsu, K Matsuzawa, M Tamura, S Tonooka, K Taniguchi, S Urasawa, J Arikawa, Azuma, I, VACCINE, 14, 6, 485, 491, Apr. 1996
English

Characterization of the nucleocapsid protein of Hantaan virus strain 76-118 using monoclonal antibodies
K Yoshimatsu, J Arikawa, M Tamura, R Yoshida, A Lundkvist, B Niklasson, H Kariwa, Azuma, I, JOURNAL OF GENERAL VIROLOGY, 77, 695, 704, Apr. 1996
English

Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus.
Akihisa Fukushima, Yung Choon Yoo, Kumiko Yoshimatsu, Kaori Matsuzawa, Mizuho Tamura, Shuichi Tono-oka, Koki Taniguchi, Shozo Urasawa, Jiro Arikawa, Ichiro Azuma., Collected papers from the Institute of Immunological Science Hokkaido University, 19, 153, 159, 1996
Hokkaido University, English

Characterization of the nucleocapsid protein of Hantaan virus strain 76-118 using monoclonal antibodies.
Kumiko Yoshimatsu, Jiro Arikawa, Mizuho Tamura, Ryu Yoshida, Lundkvist, B. Niklasson, H. Kariwa, Ichiro Azuma., Collected papers from the Institute of Immunological Science Hokkaido University, 19, 143, 152, 1996
Hokkaido University, English

Modes of Seoul virus infections: Persistency in newborn rats and transiency in adult rats
H Kariwa, M Kimura, S Yoshizumi, J Arikawa, K Yoshimatsu, Takashima, I, N Hashimoto, ARCHIVES OF VIROLOGY, 141, 12, 2327, 2338, 1996
English

Western blotting using recombinant hantaan virus nucleocapsid protein expressed in silkworm as a serological confirmation of hantavirus infection in human sera
K Yoshimatsu, J Arikawa, H Li, H Kariwa, N Hashimoto, JOURNAL OF VETERINARY MEDICAL SCIENCE, 58, 1, 71, 74, Jan. 1996
English

Production of recombinant hantavirus nucleocapsid protein expressed in silkworm larvae and its use as a diagnostic antigen in detecting antibodies in serum from infected rats
K Yoshimatsu, J Arikawa, R Yoshida, H Li, YC Yoo, H Kariwa, LABORATORY ANIMAL SCIENCE, 45, 6, 641, 646, Dec. 1995
English

EFFECT OF MDP-LYS(L18), A DERIVATIVE OF MDP, ON ENHANCING HOST-RESISTANCE AGAINST HANTAAN VIRUS-INFECTION IN NEWBORN MICE
YC YOO, K YOSHIMATSU, R HATSUSE, M TAMURA, R YOSHIDA, S TONOOKA, J ARIKAWA, AZUMA, I, VACCINE, 13, 14, 1300, 1305, Oct. 1995
English

EVIDENCE FOR THE EXISTENCE OF PUUMULA-RELATED VIRUS AMONG CLETHRIONOMYS RUFOCANUS IN HOKKAIDO, JAPAN
H KARIWA, S YOSHIZUMI, J ARIKAWA, K YOSHIMATSU, K TAKAHASHI, TAKASHIMA, I, N HASHIMOTO, AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 53, 3, 222, 227, Sep. 1995
English

Effects of muramyl dipeptide derivatives as adjuvants on the induction of antibody response to recombinant hepatitis B surface antigen.
Mizuho Tamura, Yung Choon Yoo, Kumiko Yoshimatsu, Ryu Yoshida, Tetsuya Oka, Kunio Ohkuma, Jiro arikawa, Ichiro Azuma, Collected papers from the Institute of Immunological Science Hokkaido University, 18, 155, 160, 1995
Hokkaido University, English

Effect of MDP-Lys(L18), a derivative of MDP, on enhancing host resistance against Hantaan virus infection in newborn mice.
Yung Choon Yoo, Kumiko Yoshimatsu, Rei Hatsuse, Mizuho Tamura, Ryu Yoshida, Shuichi Tono-oka, Jiro Arikawa, Ichiro Azuma., Collected papers from the Institute of Immunological Science Hokkaido University, 18, 203, 208, 1995
Hokkaido University, English

EFFECTS OF MURAMYL DIPEPTIDE DERIVATIVES AS ADJUVANTS ON THE INDUCTION OF ANTIBODY-RESPONSE TO RECOMBINANT HEPATITIS-B SURFACE-ANTIGEN
M TAMURA, YC YOO, K YOSHIMATSU, R YOSHIDA, T OKA, K OHKUMA, J ARIKAWA, AZUMA, I, VACCINE, 13, 1, 77, 82, Jan. 1995
English

CHARACTERIZATION OF THE MODE OF HANTAAN VIRUS-INFECTION IN ADULT MICE USING A NESTED REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION - TRANSIENT VIRUS-REPLICATION IN ADULT MICE
H KARIWA, M KAMIMURA, J ARIKAWA, K YOSHIMATSU, TAKASHIMA, I, N HASHIMOTO, MICROBIOLOGY AND IMMUNOLOGY, 39, 1, 35, 41, 1995
English

EFFECT OF THE SYNTHETIC LIPID A-RELATED COMPOUND, DT-5461, ON RESISTANCE TO SENDAI VIRUS-INFECTION IN MICE
R YOSHIDA, K SATO, YC YOO, K YOSHIMATSU, M TAMURA, C ISHIHARA, J ARIKAWA, AZUMA, I, IMMUNOPHARMACOLOGY, 28, 2, 153, 161, Sep. 1994
English

POSTNATAL CHANGE OF PIG INTESTINAL GANGLIOSIDE BOUND BY ESCHERICHIA-COLI WITH K99 FIMBRIAE
Y YUYAMA, K YOSHIMATSU, E ONO, M SAITO, M NAIKI, JOURNAL OF BIOCHEMISTRY, 113, 4, 488, 492, Apr. 1993
English

ANTIVIRAL ACTIVITY OF SULFATED CHITIN DERIVATIVES AGAINST FRIEND MURINE LEUKEMIA AND HERPES-SIMPLEX TYPE-1 VIRUSES
C ISHIHARA, K YOSHIMATSU, M TSUJI, J ARIKAWA, SAIKI, I, S TOKURA, AZUMA, I, VACCINE, 11, 6, 670, 674, Apr. 1993
English

Application of a recombinant baculovirus expressing hantavirus nucleocapsid protein as a diagnostic autgenin IFA test : cross reactivates among 3 serotypes of hantavirus which causes hemmorrhagic fever with renal syndrome(HFRS)."jointly worked"
Journal of Veterinary Medical Science, 55(6),1047-1050, 1993

COMPARISON OF VIRULENCE BETWEEN SEOUL VIRUS-STRAIN SR-11 AND HANTAAN VIRUS-STRAIN 76-118 OF HANTAVIRUSES IN NEWBORN MICE
YC YOO, K YOSHIMATSU, R YOSHIDA, M TAMURA, AZUMA, I, J ARIKAWA, MICROBIOLOGY AND IMMUNOLOGY, 37, 7, 557, 562, 1993
English

PROTECTIVE IMMUNITY OF HANTAAN VIRUS NUCLEOCAPSID AND ENVELOPE PROTEIN STUDIED USING BACULOVIRUS-EXPRESSED PROTEINS
K YOSHIMATSU, YC YOO, R YOSHIDA, C ISHIHARA, AZUMA, I, J ARIKAWA, ARCHIVES OF VIROLOGY, 130, 3-4, 365, 376, 1993
English

NEW METHODS FOR ISOLATION OF K99 FIMBRIAE FROM ENTEROTOXIGENIC ESCHERICHIA-COLI
K YOSHIMATSU, Y YUYAMA, E ONO, B SYUTO, M NAIKI, JOURNAL OF VETERINARY MEDICAL SCIENCE, 53, 6, 1119, 1121, Dec. 1991
English, Introduction scientific journal

ハンタウイルスエンベロープ蛋白の標的細胞への吸着・侵入における挙動の解析
森松, 組子
[北海道大学大学院医学研究科], May 2007, 1冊

組換え可溶性外被蛋白を用いたハンタウイルスワクチンおよび迅速診断キットの開発
森松, 組子
[北海道大学], Mar. 2004, 61p

微生物学実習　　　　　　　　　　　　　　　
北海道大学

スリランカにおける原因不明慢性腎臓病(CKDu)とハンタウイルス感染症の関連に関する研究　　　　　　　　　　　　　　　
森松(吉松) 組子, 2016 - Present, [Others]

腎症候性出血熱とハンタウイルス肺症候群の中和代替試験法による鑑別診断法の開発　　　　　　　　　　　　　　　
1996 - 2008

組換え可溶性外皮蛋白を用いたハンタウイルスワクチンおよび迅速診断キットの開発　　　　　　　　　　　　　　　
2001 - 2003

自然免疫情報伝達系による生体防御と胎児発生の制御～新規NFкB抑制タンパク質ファミリー分子欠損マウスの解析を中心に　　　　　　　　　　　　　　　
2003

モノクローナル抗体および細胞内抗体導入（スクレイプローディング）法を用いたハンタウイルス核蛋白の機能の解析　　　　　　　　　　　　　　　
1995 - 1996

蚕バキュロウイルス発現ハンタウイルス核蛋白の精製法の確立と診断法への応用　　　　　　　　　　　　　　　
1993 - 1993

免疫不全マウス(SCID、ヌード)での腎症候性出血熱ウイルスによる腎症候性出血熱障害の解析　　　　　　　　　　　　　　　
1992 - 1992

実験マウスにおける組換え腎症候性出血熱ウイルス蛋白を用いた免疫応答の解析－パキュロウイルスベクター発現系の新しい応用　　　　　　　　　　　　　　　
1991 - 1991

Studies on rodent-borne zoonotic diseases in Sri Lanka
Grants-in-Aid for Scientific Research
01 Apr. 2023 - 31 Mar. 2026
森松 組子, 清水 健太, 浦田 秀造
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 23K05530

Development of rapid and simple individeual diagnostic method for major infectious diseases in laboratory animals : a multiplex immunochromatographic test
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2020 - 31 Mar. 2023
土佐 紀子, 林元 展人, 石田 智子, 森松 組子
学術・科学技術の研究に供する動物の微生物モニタリングは、研究結果の信頼性の担保、および動物福祉の観点から必要不可欠である。近年、多系統少数個体維持の増加や個別換気型飼育機の普及等により、従来の微生物モニタリング方法、すなわち「おとり動物」の感染症の検出を指標とする間接的な方法では感染症を摘発することが困難となっている。この問題を解決するためには、動物を安楽死させることなく微量全血を用い、マウス、ラットの主要感染症を同時に且つ迅速・簡便に検出できる個体別血清診断法の確立が必要である。その方法として有望と考えられる「多項目イムノクロマト(ICG)法」の開発について申請者らは取り組んで来た。
本研究ではこれまでの成果を基に、１）多項目ICG法の検出条件が確定したマウス・ラットの感染症（マウス：マウス肝炎ウイルス感染症、センダイウイルス感染症、ティザー病。ラット：唾液腺涙腺炎ウイルス感染症、センダイウイルス感染症、腎症候性出血熱）の検出における本法の実用性を検証し、２）上記感染症に加え、主要感染症であるマイコプラズマ感染症（マウス、ラット）とティザー病（ラット）のICG法を確立することを目的としている。２年度（令和３年度）においては、以下の研究を実施した。
１．多項目ICGスティックの最適な保管条件・最長保管期間を明らかにする実験において、保管期間６ヶ月および１２ヶ月の多項目ICGスティックの各保管条件における検出・感度特異性への影響の結果を得た。
２．乾燥血液を用いた時のICG法の検出・感度特異性を明らかにするため、乾燥血液を作製するための条件を検討した。
３．多項目ICGスティックの輸送条件を確定するための実験設備の準備を行った。
４．Myco（マウス、ラット）とTyzzer（ラット）のICG法を確立するため、抗原の準備を行い、ICGメンブレンに塗布する抗原処理方法の実験に着手した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 20K06456

エボラ出血熱の発症の分子基盤に関する研究
科学研究費助成事業 基盤研究(C)
01 Apr. 2019 - 31 Mar. 2022
津田 祥美, 森松 組子
本課題ではエボラウイルスの主要標的細胞とされているマクロファージや肝細胞でのウイルス増殖がエボラウイルス感染症で観察される病態にどのように関与しているのか、ウイルスの組織指向性や主要標的細胞での増殖能力と致死的病態の関連性を明らかにすることを目的とする。これまでの解析によりマクロファージや樹状細胞で主に発現しているmicroRNAのターゲット配列をウイルス遺伝子に組込むことでマクロファージや樹状細胞でのウイルス増殖を抑制した組換えエボラウイルス作出可能であることを示した。また作出したウイルスは著しく病原性が減弱したことから、感染初期におけるマクロファージや樹状細胞でのウイルス増殖の重要性を示した。本研究ではクロファージや樹状細胞で増殖したウイルスが次にターゲットとし、重要な宿主応答に関与していると考えられる肝細胞でのウイルス増殖を抑制したウイルスの作成を試みた。これまでのC型肝炎ウイルスなどの研究により、肝臓で発現するいくつかのmicroRNAの重要性が報告されている。そこで本研究ではmicroRNA122をまずターゲットとして選び、microRNA122に対応する遺伝子配列を組み込んだ組換えウイルスの作出を試みた。これまでの研究と同様にマウスを用いた病原性解析を目的として、親株であるエボラウイルスとマウス馴化株に遺伝子組換えを行ったところ、ともにウイルスの作出を確認した。今後は作出したウイルスの細胞での増殖、マウスモデルを用いた病原性の解析を行う予定である。
日本学術振興会, 基盤研究(C), 北海道大学, 19K07587

熱帯性慢性腎臓病に関連する新規ハンタウイルス、ランカウイルスの解析
科学研究費助成事業 基盤研究(C)
01 Apr. 2019 - 31 Mar. 2022
森松 組子, 清水 健太, 津田 祥美
慢性腎臓病(CKD)は2002年に米国腎臓財団によって提唱された概念である。先進国では成人人口の13％を占めるとされ、そのほとんどが糖尿病や高血圧等の生活習慣病を原疾患とする。一方で、このような原疾患を持たない原因不明のCKDがスリランカ、インドの一部、中南米から報告されており、CKDuと呼ばれている。特にスリランカでは重症型のCKDuが健康な労働年齢の男性に頻発し、国家的な問題となっている。近年申請者らは、CKDu患者の約半数が抗ハンタウイルス抗体陽性であることを見いだし、ハンタウイルス感染症が慢性腎臓病の発症に関与していることを疫学的解析により示した。さらに、CKDuの流行地のげっ歯類からハンタウイルスを検出し、このウイルスが感染源となっている可能性をみいだした。本研究では、スリランカ固有の新規ハンタウイルスを解析し、この情報を基礎に血清診断法、分子生物学的診断法を開発する。さらにこれらの診断法を用いて、ヒトおよびげっ歯類におけるハンタウイルスの感染状況およびCKDu発症機序の解明を試みることを最終的な目的とする。
今年度は特に、スリランカ固有のハンタウイルスの特定と遺伝子解析を目標としていた。結果的に、存在がすでに確認されていたランカウイルスに加えてもう一つのタイランド型ハンタウイルスであるアンゾロベウイルスを見いだし、それぞれの宿主がインドハツカネズミおよびクマネズミであることを明らかにした。さらにそれぞれのウイルスの遺伝子配列を決定し、ランカウイルスは最も進化的に離れたタイランド型ハンタウイルスであること、クマネズミ由来のウイルスはマダガスカルに棲息するクマネズミ由来のアンゾロベウイルスに極めて近縁であることが明らかとなった。また、遺伝子配列を基に血清診断法および遺伝子診断法の開発を行った。
日本学術振興会, 基盤研究(C), 北海道大学, 19K10595

Molecular biological analysis of hantavirus of hantavirus relating to chronic kidney disease by unknown etiology (CKDu) in Sri Lanka　　　　　　　　　　　　　　　
U.S.-Japan Cooperative Medical Science Program Collaborative Award 2018
Apr. 2018 - Mar. 2019
MORIMATSU-Yoshimatsu Kumiko
日本医療研究開発機構, Competitive research funding

西條 政幸　　　　　　　　　　　　　　　
感染症実用化研究事業
Apr. 2016 - Mar. 2019
Masayuki Saijo
厚生労働省, Competitive research funding

Studies on host animals for leptospirosis and hantavirus infection in Sri Lanka
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2015 - 31 Mar. 2018
Yoshimatsu Kumiko, Gamage Chandika D
To clarify the mode and host of Leptospira and hantavirus infection, rat-trapping in Sri Lanka was carried out. Pathogenic strains of Leptospires were isolated from rats and shrews. And high seroprevalence (19%) of anti-hantavirus antibody among black rats was found in rural area, Girandrukotte. In Sri Lankan endemic strain of rat was considered to be a host for Thailand virus-related hantavirus. Around 50% of chronic kidney disease by unknown etiology (CKDu) patients were seropositive to hantavirus, while 5% for healthy people in CKDu non-endemic area. In this study, in Sri Lanka, it was shown that Leptospira and hantavirus infection occurred frequently from endemic rats as the infection source, and furthermore, hantavirus infection could be the risk of progression of CKDu.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 15K08796

スリランカにおけるレプトスピラ症とハンタウイルス感 染症の媒介げっ歯類に関する研究　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(C))
2015 - Mar. 2018
森松(吉松) 組子
文部科学省, Competitive research funding

Development of diagnostic methods for viral zoonoses derived from wild animals and birds and the comparative epidemiological study of the viral zoonones
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2013 - 31 Mar. 2017
KARIWA Hiroaki
In this study, simple diagnostic methods were developed for zoonoses, such as hantavirus infections, tick-borne encephalitis, and West Nile fever, which are severe and fatal diseases, and are considered as major problems in many countries. ELISA and immunochromatography were developed to detect anti-hantavirus antibodies in various rodents. ELISA systems using viral-like particles (SPs) of tick-borne encephalitis virus conjunctive with IgG and Strep-tag were established. A stable reverse genetics system for West Nile virus was developed by using homologous recombination.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 25304040

Studies on fever with unknown origin (FUO0 in South and South East Asia
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2011 - 2013
MORIMATSU Kumiko, ARIKAWA Jiro, SHIMIZU Kenta
The investigation of hantavirus-associated infectious diseases in Southeast Asia and South Asia had been conducted. Throughout the investigation, many examples of fever of unknown origin (FUO) were found from febrile diseases. In this report, it aimed to clarify FUO in this region. Febrile patient sera (not dengue fever and a flu victim) and wild rodent sera as a career of infectious agents conducted investigation of causative agent of febrile illness in Vietnam and Sri Lanka. Finally, it was suggested that seropositive cases against pathogenic organs, such as hepatitis E virus (HEV), leptospira, and hantaviruses are found from a part of FUO patient. Furthermore, it was shown that rodents in both countries also possessed these agents. Therefore rodents were able to be sources of these zoonotic agents.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Competitive research funding, 23590770

Study for preventing epidemic of viral zoonoses in Japan and theAmerican Continents
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2009 - 2012
KARIWA Hiroaki, ARIKAWA Jiro, YOSHII Kentaro, MORIMATSU Kumiko
Three novel hantaviruses were detected in Mexican rodents. The antibody detection method for various hantavirus infections was developed. Five of six monoclonal antibodies to nucleocapsid protein (NP) of Mexican hantavirus were broadly reacted with NPs of rodent-borne hantaviruses. Glycosylation of West Nile virus E protein made great influence in the pathogenesis in chicks infected with West Nile virus.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 21405035

Studies on persistent hantavirus infection in rodents; throughoutanalysis of function of immune cells
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2006 - 2008
ARIKAWA Jiro, MORIMATSU Kumiko, ENDO Rika, KARIWA Hiroaki
ハンタウイルスは持続感染齧歯類が感染源となる人獣共通感染症でヒトに腎症候性出血熱やハンタウイルス肺症候群という重篤な疾病を引き起こす。齧歯類は血中に高い中和抗体を保有しつつ不顕性にウイルスを排泄し続けるというきわめて特徴的な持続感染を成立させている。本研究では齧歯類におけるウイルス特異的CTL抑制を中心とする免疫抑制を介したハンタウイルス持続感染成立機構の詳細を明らかにすることを目的とする。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Competitive research funding, 18300136

Epidemiological study on zoonotic diseases endemic in North America which are potentially introduced into Japan
Grants-in-Aid for Scientific Research(基盤研究(B))
2004 - 2007
Hiroaki KARIWA, 高島 郁夫, 有川 二郎, 吉松 組子
In this study, new diagnostic methods were developed and the epidemiological surveys were carried out on West Nile fever and hantavirus infections which are potentially introduced into Japan.1) Development of diagnostic methods for West Nile fever: To establish the surveillance system to West Nile virus introduction to Japan, serological diagnostic methods for anti-West Nile virus antibodies were developed. The newly developed methods were the micro-neutralization test and inhibition ELISA.2) Epidemiological study of West Nile fever in wild birds in Far East Russia: Total RNA was extracted ...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 16405034

Studies on hantavirus nucleocapsid protein and envelope glycoproteins　　　　　　　　　　　　　　　
Grant-in-Aid for Scientific Research
2001 - 2007
Competitive research funding

Studies on the behavior of hantavirus envelope glycoprotein in adsorption and invasion to target cells.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2005 - 2006
MORIMATSU Kumiko
Hantaviruses are causative agents for rodent-borne viral zoonosis, HFRS and HPS. Envelope glycoproteins G1 and G2 induce neutralizing antibodies. Monoclonal antibodies possessing neutralizing activities showed fusion inhibition activities. This means vaccine target epitope for hantavirus is a fusion responsible region in envelope protein. I studied the role of envelope glycoproteins in establishment of infection in cells. At the first, we found highly sensitive cell lines (A549, BHK and VeroE6 cells) and non-permissive cell lines (MDBK) by using pseudotype VSV screening. AlphaVbeta3 integrin was reported as candidate of the cellular receptor for hantavirus entry. Therefore, we tried to induce alphaVbeta3 into MDBK. I could not detect change of infectivity in that cells. However, transfection efficiency of plasmid constract to MDBK cells were not enough to evaluate the effect of molecules. Otherwise, anti-beta3 integrin antibodies were not inhibit cellular entry of hantavirus in permissive cells found in this study. So that this molecules was considered not to be major receptor molecules in these cells. Next, I screened bindings of glycolipids from permissive cell line Vero E6 cells against hantavirus glycoprotein. Any significant binding was not detected between glycolipids and envelope proteins. These results suggested that the cellular receptor of hantavirus must be protein molecules except alphaVbeta3 integrin. Finally, a clone 5 of MDBK cells was established as relative high DNA induction and non-permissive line. And cDNA libraly from permissive cell line A5449 was produced. This study established the basis for analysis of interaction between hantavirus envelope glycoproteins and cellular molecules.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), HOKKAIDO UNIVERSITY, Competitive research funding, 17590410

アジアのヒトおよび動物におけるハンタウイルスの血清疫学的および分子疫学的研究　　　　　　　　　　　　　　　
科学技術振興調整費による中核的研究拠点（ＣＯＥ）育成
2006
アジアにおける疫学的解析を通して、ハンタウイルス感染の浸淫状況を明らかにし、新規ハンタウイルスを検索する。
Competitive research funding

Serological and molecular biological stdies on hantavirus infection among human and animals in Asia　　　　　　　　　　　　　　　
SCF System for Establishment and Support of Center's of Excellence
2006
Serological surveylance of human and animal sera and hantavirus genome analysis by using molecular biological methods
Competitive research funding

Regulation of host defense and development by innate-immunity signal transduction system
Grants-in-Aid for Scientific Research(基盤研究(B))
2003 - 2005
Masami MORIMATSU, 吉松 組子, 山本 欣郎
In innate immune system, specific pattern molecules such as LPS bind to Toll-like receptors and activate signal transduction pathway involving NF-kappaB. Recently we identified a novel nuclear IkB molecule, MAIL. In this study we focused on MAIL and other NF-kappaB related molecules.1. Analysis of MAIL deficient miceEmbryonic lethality was observed for about 90% of MAIL deficient mice. Hypoplasia of the liver was suggested to be a possible cause for this embryonic lethality. Remaining 10% of MAIL deficient mice were born alive. These mice developed severe atopic dermatitis-like disease.2. A...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 岩手大学->北海道大学, Coinvestigator not use grants, Competitive research funding, 15380201

ハンタウイルス核蛋白およびエンベロープ蛋白の構造と機能に関する研究　　　　　　　　　　　　　　　
科学研究費補助金
Apr. 2001 - Mar. 2004
森松(吉松)組子
組換え蛋白を用いて粒子形成、出芽、細胞への侵入の感染サイクルにおける構造蛋白の役割を解析する
文部科学省, Competitive research funding

Development of hantavirus vaccine and rapid diagnosis kit by using soluble recombinant envelope glycoproteins
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2001 - 2003
MORIMATSU Kumiko, ONO Eriko, MORIMATSU Masami, KARIWA Hiroaki, ARIKAWA Jiro
1. It was clarified that recombinant Hantavirus envelope glycoproteins G1 and G2 (GPs) had the cell-fusion activity by using CAG promotor-expression system. Fusion-responsible epitope on GPs was found to locate in the neutralization (FRNT)-relating epitope. Therefore, the recombinant GPs was considered to possess neutralization-and fusion-relating epitopes. In addition, hantavirus nucleocapsid (N) protein was also expressed in mammalian cells by using same vector. As the result the N protein may suppress that expression and transportation of the envelope protein. It was also shown that the virus like particle was not formed by GPs and N protein alone.
2. By using recombinant GPs, pseudotype vesicular stomatitis virus (VSV) enveloped with hantavirus GPs altered to VSV G protein was produced (VSVΔG*HTN). Similar pseudotype VSV was produced with recombinant GPs of Seoul virus (VSVΔG*SEO). These pseudotypes were applied to rapid neutralization assay as safety alternatives of authentic viruses. These pseudotype virus particles were also applied to vaccination as alternatives to authentic virion. Mice were immunized with soluble recombinant GPs or pseudotype virion. In mice immunized with soluble recombinant GPs, FRNT antibody was not detected. Contrary, in mice immunized with VSVΔG*HTN virion, FRNT antibody was detected. Challenge administration of hantavirus was carried out by s.c. inoculation of 4 FFU of hantavirus. These mice did not show the elevation of anti-N antibody and hantavirus specific CD8 T cell response, indicating that the FRNT antibody could protect mice from hantavirus infection. On the other hand, all control mice immunized with VSVΔG*G or PBS could not escape from hantavirus infection. These results indicated that packaged recombinant GPs on VSV particle were possible to induce protective FRNT antibody. This study shows that novel approach for the development of vaccination of viruses that have difficulties in preparation of authentic virus particles.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Competitive research funding, 13556046

Study for the development of new gene targeting method utilizing epitope tags
Grants-in-Aid for Scientific Research(基盤研究(B))
1999 - 2001
Masami MORIMATSU, 吉松 組子, 小川 和重, 首藤 文榮, 吉村 佳典, 三好 一郎
To establish the bases for developing new methods of gene targeting, we investigated the efficiency of gene knock-in and the use of specific markers called epitope-tags. By using this approach, gene of interest is to be analyzed by antibodies against epitope-tags. We selected some genes for targeting experiments. Detailed characterization of candidates for epitope-tags was also carried out.1. Investigation of a novel endotoxin-inducible gene, MAIL, as a target.MAIL is suitable for targeting experiment because it is known that transcription of the gene is markedly up-regulated by endotoxin s...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 岩手大学, Coinvestigator not use grants, Competitive research funding, 11556064

Studies on the development of diagnosis for infectious diseases among laboratory rodents
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
1999 - 2001
ARIKAWA Jiro, MORIMATSU Kumiko, KARIWA Hiroaki, SATO Hiroshi, TAKAKURA Akira
1. Nucleocapsid (N) proteins of Hantaan, Seoul and Dobrava viruses were expressed by E. coli and baculovirus systems. The recombinant proteins by both systems produced enough amount of recombinant proteins and retained the anti genicity similar to those of authentic viruses. They are considered to be a ble to apply for ELISA antigen.
2. The truncated N proteins which lacked 50 amino acids at N-terminal reduced the cross reactivity to antibody to heterologous serotypes. Therefore, the truncated antigens were applied as serotyping antigen.The ELISA with the truncated antigen able to serotype of patient and rodent sera from China and Far Eastern part of Russia as determined by ordinary neutralization test.
3. Mouse hepatitis virus N protein gene was expressed by yeast system of which maximum expression was observed at 72 hours after culture. However, the antigenicity was too low to apply for ELISA antigen.
4. cDNA of N protein of lymphocytic choriomeningitis (LCM) virus were cloned from Japanese isolate (strain OQ28) and prototype strain (strain WE). The cDNAs of full length, C-terminal region and central region were independently transfected to COS cells. Although they could express recombinant proteins, amount of antigen expressed was too small to apply to ELISA.
5. Recombinant baculovirus expressing LCM virus N protein was provided from National Institute of Infectious Diseases Japan. Both the recombinant baculovirus infected SF-9 cells and Tm5 cells were found to be applicable for IFA antigen and ELISA antigen, respectively. A total of 9,840 mouse sera from 1,117 animal facility in Japan were tested for LCM virus antibody by IFA and ELISA. From these results, screening with ELISA followed by confirmation by IFA was recommended.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Competitive research funding, 11558096

実験動物での賢症候性出血熱とハンタウイルス肺症候群の鑑別診断法の確立に関する研究
科学研究費助成事業 奨励研究(A)
1999 - 2000
森松 組子
本研究はハンタウイルスの侵入を阻止するために齧歯類における診断法、特にHPS感染を摘発する方法を確立することを目的とする。ハンタウイルスの抗原性は大きく3つに分けられる.ネズミ亜科(Murinae)、ハタネズミ亜科(Microtinae/Arvicolinae)、アメリカネズミ亜科(Sigmodontinae)それぞれに属する齧歯類を宿主とするウイルスである.本年度はさらに応用範囲を拡大し、さらに鑑別診断系の評価を行った。
1.平成11年度に引き続き野鼠血清の収集を行った。本年度はHPSのreservoir動物となるアメリカネズミ亜科のげっ歯類の血清および抗血清を入手することができた。さらにより多くのネズミ亜科、ハタネズミ亜科のげっ歯類血清合計31種について適切な抗体検出系を決定することができた。この結果からより広範な抗体摘発体制を取ることが可能となった。
2.平成11年度に引き続き、Hantaan,Puumala,SinNombreハンタウイルスに対する標準抗血清の作成を行った。
3.3種類のハンタウイルス、Hantaan,Puumala,SinNombreハンタウイルス核蛋白の抗原性の交差は少ないことが明らかとなった。
4.ネズミ亜科のウイルス3種類(Hantaan,Seoul,Dobrava)の核蛋白をコードするcDNAから主要共通抗原領域をコードする部分を削除し、バキュロウイルスベクターを用いて発現させることで調整した抗原を用いた鑑別診断法の感度は約95%、特異性は100%であり、十分な感度と特異性を示した。
以上の結果から、ハンタウイルスの侵入を阻止するために、広範な野鼠の抗体検出法、適切な抗原を供給することが可能となった。さらにネズミ亜科のハンタウイルスについては詳細なウイルス型別も可能な診断系を提供できることが明らかとなった。
日本学術振興会, 奨励研究(A), 北海道大学, Competitive research funding, 11780601

Molecular biologic characterization of hatavirus pathogenicity
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).
1999 - 2000
ARIKAWA Jiro, MORIMATSU Kumiko, KARIWA Hiroaki, TAKASHIMA Ikuo, MORIKAWA Shigeru
1. Epidemiologic conditions and status of vaccine development in China were investigated. Information regarding to nucleotide sequence of Chinese isolates and diagnostic procedures for serodiagnosis were exchanged.
2. Technical information for genetic characterization of hantavirus was obtained from Slovak scientist.
3. Technical information for characterization of hantavirus receptor and genetic reassortant virus was obtained from US scientist.
4. Techniques for construction of artificial hantavirus was obtained from scientist of Wisconsin University School of Veterinary Medicine.
5. Information regarding to Nephropathia epidemica virus pathogenicity was obtained from Dr.Antti Vaheri of Helsinki University.
6. Information of epidemiologic and epizootiologic conditions in South East Asia was obtained from scientist in Thai.
7. Infection enhancement by the GalNac specific lectin, DBA and SBA was confirmed. Involvement of cellular factor on the virus cell membrane fusion was elucidated.
8. Pathogenicity to mice was related to growth rated at peripheral cite. The difference was considered to caused by the point mutation at enveloped protein.
9. Viral S and M genome was cloned and expressed in the mammalian cells. Several kinds of mini-genomes were constructed for the examination of role for transcription and translation. For the next step, relationship between the minigenome expression and the proteins expressed by S and M genomes will be required.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B)., Hokkaido University, Competitive research funding, 11694228

Studies on a mechanism of hantavirus persistent infection in central nervous system and immune system
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A).
1998 - 2000
ARIKAWA Jiro, MORIKAWA Shigeru, KARIWA Hiroaki, MORIMATSU Kumiko
1. Hantavirus infection was enhanced about 10 times by addition of lectins (DBA and SBA) which specifically bind to N-acetylgalactosamine. This enhancement was considered to caused by the cross linking between receptor to virion by the lectins.
2. Two Vero E6 cell subclones, one induce low pH dependent cell fusion after hantavirus infection and the other resistant to cause cell fusion, were established. By using the two cell clones, the possible role for the cellular factor for responsible for induce infected cell fusion was considered.
3. After peripheral infection of hantavirus to mice, virulent virus reached to brain 4 to 5 days earlier than that of avirulent virus. This difference was considered as a mechanism which define the virulence of hantavirus in the mouse model.
4. Virulent hantavirus showed higher growth rate in the brain micro vascular cells and peritoneal macrophage, suggesting that virulence relates to the growth ability in the target organs.
5. Genetic reassortant virus between virulent and avirulent viruses were established. The comparison of the virulence of the reassortant viruses indicated that one amino acid difference at enveloped protein and nucleotide difference in the polymerase gene are related to the virulence.
6. Virulent hantavirus infected SCID mice were passively transferred with spleen cells of immunized BALB/c mice 3 weeks after infection. The recipient SCID mice represented apparent weight loss 4 days after the transfer, indicating the immune mediated pathogenicity.
7. Hantaan virus S and M genome segment which encoding nucleocapsid protein and enveloped glycoprotein, respectively were cloned and expressed in the mammalian cells.
8. Entire L genome segment which encodes polymerase was cloned. The expression of the L clone is under going.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A)., Hokkaido University, Competitive research funding, 10306019

Comparative ecological study of hantavirus in rodents in Japan and Far East Russia
Grants-in-Aid for Scientific Research(基盤研究(C))
1998 - 1999
Hiroaki KARIWA, 吉松 組子, 水谷 哲也, 有川 二郎, 高島 郁夫
Epidemiological study was conducted in Japan and Far East Russia and the followings were revealed.1. Hantavirus was identified in the urine from infected rats. Since newborn rats intranasally inoculated with the urine containing virus had the virus in their organs and urine, the virus may be maintained by the transmission with virus-contaminated urine by intranasal route in nature.2. Enzyme linked immunosorbent assay (ELISA) using baculovirus-expressed nucleocapsid proteins of different hantaviruses as antigens was established. This assay made it possible to detect hantaviral antibody and a...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 10660296

免疫カセットセオリーに基づくハンタウイルス核蛋白高度保存領域での感染防御免疫誘導
科学研究費補助金(奨励研究(A))
1997 - 1998
森松 組子
ハンタウイルスは腎症候性出血熱の原因ウイルスで、ブニヤウイルス科に属するRNAウイルスである。この研究ではハンタウイルス内部蛋白の特定のエピトープを標的抗原とする新しいタイプのペプチドワクチンの開発を目的として、マウス実験感染モデルを用いて単クローン抗体E5/G6エピトープペプチドの誘導する免疫応答とその感染防御活性について検討している。平成10年度は、カセット配列(主要組織適合抗原結合領域)を付加した,E5/G6エピトープのペプチド抗原による免疫応答の解析を明らかにするために、ペプチドを合成しマウスに免疫し免疫応答を測定することを試みた。1. ペプチドデザインPeptide 1 YEGF-EDVNGIRKP-KAKGITPeptide 2 YEGFS-EDVNGIR---KAKGITをMAP及び通常のペプチドとして合成した。これはH-2bのカセット配列に、E5G6エピトープ配列EDVNGIRKPKを挿入したものである。2. 免疫MAPのペプチド抗原を100ug/mouse complete adjuvantとともにC57BL6マウスに免疫し、経時的に採血し、抗体価の上昇を調べた。3. T細胞応答の測定系の確立牌臓細胞をX線照射によって不活化し、抗原提示細胞として用いることを試みた。昨年度の研究結果から非RI測定系を確立するため代替法として、市販のテトラゾリウム塩類、酵素を比...
文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 09780775

Studies on the control of hantavirus infection and rodent
Grants-in-Aid for Scientific Research(国際学術研究)
1996 - 1997
Jiro ARIKAWA, 宋 干, 李 徳新, Antti Vaheri, Bo Niklasson, 網 康至, 伊勢川 裕二, 五十嵐 章, Clarence Pet, 杉山 和良, 高島 郁夫, 森松 組子, 王 華, Clarence Peters
Japanese investigator, Dr. Sugiyama carried out a epizootiologicstudy of wild rodents at Beijing and Xian city. A total of 100 rodents were captured from the two regions and were examined for their antibody and antigen distribution.Chinese investigator, Dr. Li, stayed at Japanese research institution for examining genetic comparison among Chinese hantaviruses obtained from above materials. He examined partial nucleotide sequence of two Chinese isolates and showed the higher relationship to Korean isolates than to Japanese one.Finish investigator, Dr. Vaheri, visited at Japanese investigator...
Ministry of Education, Culture, Sports, Science and Technology, 国際学術研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 08044227

Establishment of serodiagnostic method and surveylance system for hemorrhagic fever with renal syndrome virus infection in experimental animals
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
1994 - 1996
ARIKAWA Jiro, TAKAKURA Akira, SUGIYAMA Kazuyoshi, YOSHIMATSU Kumiko, KARIWA Hiroaki
1. Recombinant baculovirus expressing hantavirus nucleocapsid protein (Bac.HTN-NP) was applied for the antigen of ELISA.Specificity of the ELISA was the same to that of the IFA which uses infected Vero E6 cells as antigen. However, the ELISA had a sensitivity problem because of the relatively high background coloring.
2. cDNA which encoded hantavirus nucleocapsid protein was expressed by using E.coli system and established capture ELISA system. This ELISA was shown to have same specificity and sensitivity to that of the ordinally IFA,and therefore, considered as a useful screening method.
3. Bac.HTN-NP was successfully applied for the antigen for Western blotting (WB). The WB method readily distinguished specific reaction from nonspecific reaction from the WB pattern. Therefore, the WB was considered as an effective method for the serologic confirmation of hantavirus infection.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 06558112

細胞内抗体導入(スクレイプロ-ディング)法でのハンタウイルス核蛋白の機能の解析
科学研究費補助金(奨励研究(A))
1995 - 1995
吉松 組子
ハンタウイルスは腎症候性出血熱の原因ウイルスで、ブニヤウイルス科に属するRNAウイルスである。この研究ではハンタウイルス核蛋白の誘導する液性抗体の感染防御について明らかにすることを目標として感染防御に有効なエピトープ領域の決定を行なった。1次構造上の抗原領域の決定; 大腸菌を使ってハンタウイルスHantaan 76-118株の核蛋白の様々な部分を組換え蛋白として発現させ、単クローン抗体との反応性を調べ、単クローン抗体の認識部位を明らかにした。リニアエピトープを認識する単クローン抗体E5/G6についてはcDNAから予想されるアミノ酸配列を元にペプチドを合成し反応性を確認し、エピトープの特定を行なったところ,アミノ酸166-175の配列,EDVNGIRKPKであることが明らかとなった。またこの実験に付随して,ハンタウイルスの核蛋白のアミノ酸1から103がimunodominant領域であることが分かった.すなわち,人及び動物がハンタウイルスに感染したとき,核蛋白に対する抗体が強く誘導されるが,そのほとんどのリニアエピトープはこの領域に集まっていることが明らかとなり,診断抗原として有用な領域であることが分かった。また、立体構造依存性のエピトープについては,バキュロウイルスでの同様の実験から,この1-103の領域と200-300の領域にもにも存在することが示唆された。スクレープロ-デ...
文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 07856033

Studies on development of HFRS vaccine and therapeutics
Grants-in-Aid for Scientific Research(国際学術研究)
1993 - 1995
Jiro ARIKAWA, Bo Niklasson, 宋 干, 杉山 和良, 橋本 信夫, Niklasson Bo, 周 桂珍, 森松 組子, Ake Lundkvis, Bo Niklasson
1.In 1993 and 1995, head investigator (Dr. Arikawa), and Japanese investigators (Drs. Hashimoto, Morimatsu, Kariwa) visited Swedish Institute for Infectious Disease control, and Helsinki University Institute for Virology and made information exchange and discussions along with this research project.2.In 1993, Chinese investigators (Dr. Song and Hun), in 1995, Swedish investigators (Drs. Niklasson and Lundkvist) visited institutions of Japanese investigator such as Hokkaido University, National Institute Health of Japan and Osaka University to do information exchange and discussions along wi...
Ministry of Education, Culture, Sports, Science and Technology, 国際学術研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 05044144

組換えハンタウイルス核蛋白を用いたRNPトランスフェクション系の確立
科学研究費補助金(奨励研究(A))
1994 - 1994
吉松 組子
これまでに、私は蚕のバキュロウイルス系を用いて、ハンタウイルスの核蛋白を大量に発現するシステムを開発してきた.今回の研究では、この組換え蛋白を用いて、RNPトランスフェクション系を確立する事を目的とした.ハンタウイルス核蛋白を蚕のヘモリンフ中に発現させた場合、不溶性となる.この不溶性蛋白は、尿素及びグアニジン塩酸塩で可溶化され、特に尿素存在下で陰イオン交換クロマトグラフィーを行った場合、可溶性の蛋白として精製が可能である.しかしながら、この蛋白は消化を受け、フラグメント化されている場合が多い.これをさらに精製し、全長の核蛋白のみを精製するため、核蛋白に対するモノクローナル抗体を使ったAffinity精製を試みた.結果は収率は著しく低いものの、全長を含む核蛋白も精製が可能であった.しかしながら、これらの核蛋白に対するモノクローナル抗体を用いて精製した場合、それぞれの抗体の認識部位によって精製されるフラグメントが異なる.このため、これらの抗体の一次構造上の認識部位を決定しておく必要が生じた.また、Derai et alは大腸菌による発現組換え蛋白がRNA結合能を保持していたことを報告している.このため、大腸菌の発現系を利用し、抗原部位の決定を試みた.結論は、比較的効率よく全長の組換え蛋白を精製できるモノクローナル抗体は、立体構造認識の一部の単クローン抗体と、N末端を認識する抗体で...
文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 06760274

蚕バキュロウイルス発現組換えハンタウイルス核蛋白の精製法の確立と診断法への応用
科学研究費補助金(奨励研究(A))
1993 - 1993
森松 組子, 吉松 組子
1.感染蚕ヘモリンフ中の不溶性画分を遠心洗浄することによって、組換え蛋白を部分精製、濃縮を行った。この不溶性画分は、弱アルカリ性(pH8.0)、還元条件下で、4M Guanidin Hydrochrolide, 6M Urea,あるいは1%SDS等によって可溶化された。ここから可溶化のための物質を取り除くと再び不溶性の沈殿となった。尿素存在下の陰イオン交換クロマトグラフィーを行なったところ、0.15-0.2MのNaClで核蛋白は溶出され、この画分は50mM Tris-HCl pH8.0、または水に透析後も再沈殿することはなかった。しかしながらこの時、リン酸を含む緩衝液に透析すると沈殿を生じることが分かったので、以下Tris系の緩衝液を用いることとした。この可溶化核蛋白を含む画分は室温で取り扱うと断片化が生じ、これはセリンプロテアーゼ阻害剤であるPMSFを加えて4℃で取り扱うことによって妨げることが明かとなった。2.可溶化され、濃縮された組換え核蛋白は単クローン抗体を結合させたアフィニティーカラムを用いてさらに精製することが可能であった。この抗原をHigh-density Particleに結合させ凝集抗原の作製を試みた。しかしながら抗原を感作させるだけでParticleは凝集した。塩析では10%飽和硫安で沈殿し、しばしば不溶化した。これらの結果は、アミノ酸配列からも予想されて...
文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 05760237

Genetical and biochemical characterizations of hemorrhagic fever with renal syndrome virus infection in mice.
Grants-in-Aid for Scientific Research(試験研究(B))
1991 - 1993
Jiro ARIKAWA, 伊勢川 裕二, 石原 智明, 吉松 組子, 板倉 智敏, 橋本 信夫
1. SCID mice inoculated i.p. with Hantaan virus and Seoul virus developed systemic infection and died after 32 to 38 days post infection.2. Viral antigen was detected from various organs including kidney. Although no hemorrhagic manifestations was seen in kidney, the SCID mice showed increased level of BUN after infection.3. RT-PCR followed by Nested-PCR method was established for detecting Hantaan virus genome in various organs in infected mice.4. SCID mice (21 days post infection) were passively administered with spleen cells which were prepared from normal BALB/c mice. Seven days after t...
Ministry of Education, Culture, Sports, Science and Technology, 試験研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 03558009

STUDIES ON THE DEVELOPMENT OF HEMORRHAGIC FEVER WITH RENAL SYNDROME VACCINE USING RECOMBINANT BACULOVIRUS EXPRESSED PROTEIN.
Grants-in-Aid for Scientific Research(一般研究(C))
1990 - 1992
Jiro ARIKAWA, 吉松 組子, 高島 郁夫, 橋本 信夫
1) All the neutralizing monoclonal antibodies to Hantaan virus envelope proteins examined so far caused antibody-dependent enhancement of infection to macrophage cell lines with subneutralizing amount of the antibodies. Thus, it seemed to be difficult to separate neutralization specific antigens for preparation of vaccine.2) Recombinant Hantaan virus envelope proteins were successfully expressed by the baculovirus expression system to prepare the viral antigens without any biological hazard from the Hantaan virus infection. The antigenic properties of the expressed and authentic viral antig...
Ministry of Education, Culture, Sports, Science and Technology, 一般研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 02806056

腎症候性出血熱ウイルス(ハンタウイルス)の病原性に関する研究　　　　　　　　　　　　　　　
科学研究費補助金
Competitive research funding

Study on Virulency and pathogenicity of hantavirus, which causes hemorrhagic fever with renal syndrom　　　　　　　　　　　　　　　
Grant-in-Aid for Scientific Research
Competitive research funding