博士（獣医学）, 北海道大学

Doctoral (PhD) degree program, Graduate School of Infectious Diseases

Integrated in vivo and transcriptomic analyses of lethal Oropouche virus infection reveal suppression of pathogenic host responses by antiviral therapy
Cássia Sousa Moraes; Gabriel Gonzalez; Akihiko Sato; Shigeru Miki; Atsuko Inoue; Koshiro Tabata; Joshua W. Kranrod; Chilekwa Frances Kabamba; Aiko Ohnuma; Keita Matsuno; Rio Harada; Shinji Saito; Michihito Sasaki; Yasuko Orba; William W. Hall; Hirofumi Sawa; Yukari Itakura
16 Mar. 2026

Epidemiological, clinical, and virological characterizations of Yezo virus infections, an emerging tick-borne orthonairovirus disease in Japan.
Hiroki Yamaguchi; Keita Mizuma; Kei Watari; Yuma Ohari; Kazuya Mitsuhashi; Kazuma Tamiya; Nijiho Kawaguchi; Yasuko Orba; Masayuki Saijo; Keita Matsuno
The Journal of infectious diseases, 10 Feb. 2026, [International Magazine]
English, Scientific journal, BACKGROUND: Febrile disease caused by infections of Yezo virus (YEZV), a tick-borne orthonairovirus, was first reported in Japan in 2021 and subsequently identified in China. While the recent studies suggest a broader endemic area of the emerging YEZV infections, its clinical and epidemiological characteristics remain poorly elucidated due to the limited number of reported cases. METHODS: We conducted retrospective and prospective surveillance of patients with suspected tick-borne febrile illnesses in Hokkaido, Japan, between 2013 and 2024. Serum samples were analyzed by RT-qPCR, IgM/IgG ELISA, and neutralization assay. Viral genome of isolates was sequenced and phylogenetically analyzed with publicly available YEZV genomes. RESULTS: A total of 22 patients with YEZV infections including 10 newly identified patients was analyzed. Most infections occurred between May and July, coinciding with the peak activity of Ixodes ticks in the study area. A case from southern Hokkaido was firstly identified. Fever, leukocytopenia, thrombocytopenia, elevated levels of liver enzymes, and ferritin were determined as common features observed in patients with YEZV infections. Viral RNA was typically detectable in the serum within 7 days after the disease onset. Serum antibodies became positive later and might persist up to at least 600 days. Phylogenetic analysis incorporating five new isolates showed the circulations of two genetic groups of YEZVs in Japan. CONCLUSIONS: Our results revealed characteristics of YEZV infections in patients and highlighted the importance of combination of molecular and serological diagnostics. The proposed case definitions and diagnostic framework may contribute future surveillance.

Spatial distribution of ticks and tick-borne pathogens in central Hokkaido, Japan and associated ecological factors revealed by intensive short-term survey in 2024
Mebuki Ito; Yuma Ohari; Mai Kishimoto; Keita Matsuno
openRxiv, 06 Feb. 2026
Tick-borne pathogens are transmitted by tick bites to cause infectious diseases in humans and domestic animals. To anticipate the occurrence of tick-borne diseases, it is required to understand high resolution distribution of infection risk and associated ecological factors. The aim of the present study is to reveal the spatial distribution of ticks and ticks infected with pathogens in central Hokkaido, Japan. Adult and nymphal ticks were collected with a constant effort at 171 sites from 13 May to 26 June 2024, followed by screening tick-borne pathogens. The potential suitable habitats of seven tick species and the endemic tick-borne pathogens in the study area (i.e. tick-borne encephalitis virus, Yezo virus, Beiji nairovirus, Lyme disease group borreliae, and relapsing fever group borreliae) were predicted using ecological niche modeling. Ixodes persulcatus and Ixodes ovatus were identified as the primary ticks to determine the distributions of all the pathogens. Besides, the predicted suitable habitats were specific to each pathogen/tick species. Among the environmental variables considered for modeling, snow depth appeared to significantly contribute to the distribution differences between ticks and pathogens. The findings of this study expand our understanding of the spatial risk distribution of tick-borne pathogen infections and its ecological context.

Oita virus rediscovered after 50 years: isolation of genetically conserved strains from bats in Southern Japan
Saiko Sawai; Kittiya Intaruck; Sho Sata; Mana Esaki; Kimitake Funakoshi; Shin Murakami; Keita Matsuno; Ryo Nakao; Kazunori Kimitsuki; Takaaki Yahiro; Akira Nishizono; Naganori Nao; Yasuko Orba; Ayato Takada; Masahiro Kajihara; Makoto Ozawa; Kosuke Okuya
Microbiology Spectrum, American Society for Microbiology, 11 Nov. 2025
Scientific journal, ABSTRACT

Bats are natural reservoirs of numerous viruses, including members of the Rhabdoviridae family. Oita virus (OITV), classified within the genus Ledantevirus , was first isolated from the blood of a Japanese horseshoe bat ( Rhinolophus cornutus ) in the Oita Prefecture, Japan, in 1972. However, since then, no other OITV isolates have been reported. In this study, we isolated two OITV strains—OITV 321/2022 and OITV 326/2022—from oral swab samples of R. cornutus collected in the Katano Cave, Kagoshima Prefecture, Japan. Genetic analysis revealed >98% nucleotide identity with the previous isolate, OITV 296/1972. Phylogenetic analysis confirmed their classification within the Ledantevirus subgroup C. We assessed viral growth kinetics using 17 cell lines from diverse animal species, including bats, rodents, humans, and arthropods. OITV 321/2022 showed efficient replication in primate-derived, bat-derived, and human-derived cells, but not in tick or mosquito cell lines. Experimental infection of BALB/c mice demonstrated that OITV 321/2022 induced no overt clinical signs via either the intracerebral or intranasal routes. However, systemic infection and viral replication in the brain and lungs were observed by intracerebral inoculation. Intranasal inoculation with OITV 321/2022 and OITV 296/1972 resulted in transient pulmonary infection without systemic dissemination. This study provides evidence of OITV circulation in wild bat populations over 50 years, highlighting the need for continued surveillance of bat-associated rhabdoviruses in Japan.

IMPORTANCE

Bats are known reservoirs of zoonotic viruses, and their proximity to humans raises concerns regarding zoonotic risks. We report the first isolation of the Oita virus (OITV), a bat-associated ledantevirus, that has circulated for over 50 years. Unlike a previous blood-derived isolate, our isolates were obtained from oral swabs, suggesting their potential for respiratory transmission. OITV could infect a wide range of mammalian cells, including human-derived cells, and induce systemic infection in mice without clinical symptoms. These findings indicate that OITV possesses a broad host tropism and may circulate among microbats through the respiratory tract. Although the pathogenicity of the newly isolated strain appears to be attenuated compared with that of a historical brain-passaged strain, its ability to replicate in human cells underscores its potential zoonotic relevance, necessitating active surveillance and functional characterization of bat-derived rhabdoviruses to better assess emerging infectious disease threats.

Molecular and Functional Characterization of Sika Deer ACE2 as a Receptor for SARS-CoV-2.
Anastasiia Kovba; Manabu Igarashi; Keita Mizuma; Yuma Ohari; Manabu Onuma; Michito Shimozuru; Kotaro Shimizu; Masami Yamanaka; Keita Matsuno; Toshio Tsubota
Microbiology and immunology, 69, 11, 533, 543, Nov. 2025, [International Magazine]
English, Scientific journal, Surveillance of SARS-CoV-2 in white-tailed deer (WTD, Odocoileus virginianus) has revealed its widespread and sustained transmission across North America, with evidence suggesting possible transmission from deer to humans. In the following surveillance studies in other deer species, however, little evidence of infection spread was found, including in sika deer (Cervus nippon) in our previous study. Differences in the structure of the virus entry receptor angiotensin-converting enzyme 2 (ACE2) are known to act as one of the functional barriers to SARS-CoV-2 infection. To investigate the molecular basis of the lack of SARS-CoV-2 transmission to sika deer, we performed structural and functional analyses of the sika deer ACE2 in comparison with WTD ACE2. Comparison of sika deer ACE2 sequence and those of cervid species with WTD ACE2, followed by in silico molecular dynamics analysis, revealed a substitution of lysine to asparagine in position 31 commonly found in cervid ACE2s can potentially alter binding to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD). Functional assays in cells expressing sika deer and WTD ACE2s showed minimal differences in viral binding and replication, demonstrating that SARS-CoV-2 can similarly utilize ACE2 from both species. These findings suggest that sika deer and possibly other cervids may be highly susceptible to SARS-CoV-2 and highlight the need to investigate other factors impacting virus spread in deer populations.

Phylogenetic position of the northern pika Ochotona hyperborea in Hokkaido, Japan based on mitochondrial COI sequences
Tomoki Sakiyama; Shumpei Kamiyama; Kuniko Kawai; Yuma Ohari; Keita Matsuno; Satoshi D. Ohdachi
MAMMAL RESEARCH, 70, 3, 399, 405, Jul. 2025
English, Scientific journal

A protein language model for exploring viral fitness landscapes
Jumpei Ito; Adam Strange; Wei Liu; Gustav Joas; Spyros Lytras; Keita Matsuno; Naganori Nao; Hirofumi Sawa; Keita Mizuma; Isshu Kojima; Jingshu Li; Tomoya Tsubo; Shinya Tanaka; Masumi Tsuda; Lei Wang; Yoshikata Oda; Zannatul Ferdous; Kenji Shishido; Takasuke Fukuhara; Tomokazu Tamura; Rigel Suzuki; Saori Suzuki; Shuhei Tsujino; Hayato Ito; Yu Kaku; Naoko Misawa; Arnon Plianchaisuk; Ziyi Guo; Alfredo A. Hinay; Kaoru Usui; Wilaiporn Saikruang; Keiya Uriu; Yusuke Kosugi; Shigeru Fujita; Jarel Elgin M.Tolentino; Luo Chen; Lin Pan; Wenye Li; Mai Suganami; Mika Chiba; Ryo Yoshimura; Kyoko Yasuda; Keiko Iida; Naomi Ohsumi; Shiho Tanaka; Kaho Okumura; Kazuhisa Yoshimura; Kenji Sadamas; Mami Nagashima; Hiroyuki Asakura; Isao Yoshida; So Nakagawa; Akifumi Takaori-Kondo; Kotaro Shirakawa; Kayoko Nagata; Ryosuke Nomura; Yoshihito Horisawa; Yusuke Tashiro; Yugo Kawai; Kazuo Takayama; Rina Hashimoto; Sayaka Deguchi; Yukio Watanabe; Yoshitaka Nakata; Hiroki Futatsusako; Ayaka Sakamoto; Naoko Yasuhara; Takao Hashiguchi; Tateki Suzuki; Kanako Kimura; Jiei Sasaki; Yukari Nakajima; Hisano Yajima; Takashi Irie; Ryoko Kawabata; Kaori Sasaki-Tabata; Terumasa Ikeda; Hesham Nasse; Ryo Shimizu; MST Monira Begum; Michael Jonathan; Yuka Mugita; Sharee Leong; Otowa Takahashi; Kimiko Ichihara; Takamasa Ueno; Chihiro Motozono; Mako Toyoda; Akatsuki Saito; Maya Shofa; Yuki Shibatani; Tomoko Nishiuchi; Jiri Zahradni; Prokopios Andrikopoulos; Miguel Padilla-Blanco; Aditi Konar; Kei Sato
Nature Communications, 16, 1, Springer Science and Business Media LLC, 13 May 2025
Scientific journal

Epidemiological Characteristics of Severe Fever with Thrombocytopenia Syndrome.
Sakarn Charoensakulchai; Keita Matsuno; Emi E Nakayama; Tatsuo Shioda; Hisham A Imad
The American journal of tropical medicine and hygiene, 112, 5, 956, 962, 07 May 2025, [International Magazine]
English, Scientific journal, Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease primarily reported in Asia. This review aims to summarize studies on the epidemiological characteristics of SFTS. Literature from PubMed and Scopus was searched up to February 14, 2024. A total of 76 articles were eligible. Infections were reported in China, Japan, South Korea, and several other countries in Asia. The incidence of SFTS has been rising and reported from new areas across Asia. The incidence rate was highest in China, ranging from fewer than 0.1 to 4.2 cases per 100,000 population and reaching up to 127.6 cases per 100,000 population in some areas. Most cases occurred between April and December. Elderly farmers and veterinarians were the most affected group. Key epidemiological factors included direct contact with animals, outdoor work, vegetation near homes, rural or hilly residency, tick bites, and direct contact with blood or saliva from infected animals or humans.

Application of versatile reverse genetics system for feline coronavirus
Izumi Kida; Tomokazu Tamura; Yudai Kuroda; Takasuke Fukuhara; Ken Maeda; Keita Matsuno
Microbiology Spectrum, American Society for Microbiology, 10 Mar. 2025, [Last author, Corresponding author]
Scientific journal, ABSTRACT

Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV). Although multiple gene mutations in FCoV likely account for FIP pathogenesis, molecular studies for FCoV have been limited due to the lack of a suitable reverse genetics system. In the present study, we established a rapid PCR-based system to generate recombinant FCoV using the circular polymerase extension reaction (CPER) method for both serotype 1 and 2 viruses. Recombinant FCoV was successfully rescued at sufficient titers to propagate the progeny viruses with high sequence accuracy. The growth kinetics of recombinant FCoV were comparable to those of the parental viruses. We successfully generated recombinants harboring the spike gene from a different FCoV strain or a reporter HiBiT tag using the CPER method. The chimeric virus demonstrated similar characteristics with the parental virus of the spike gene. The reporter tag stably expressed after five serial passages in the susceptible cells, and the reporter virus could be applied to evaluate the sensitivity of antiviral inhibitors using the luciferase assay system to detect HiBiT tag. Taken together, our versatile reverse genetics system for FCoV shown herein is a robust tool to characterize viral genes even without virus isolation and to investigate the molecular mechanisms of the proliferation and pathogenicity of FCoV.

IMPORTANCE

Feline infectious peritonitis is a highly fatal disease in cats caused by feline coronavirus variants that can infect systemically. Due to the lack of a versatile toolbox for manipulating the feline coronavirus genome, an efficient method is urgently needed to study the virus proteins responsible for the severe disease. Herein, we established a rapid reverse genetics system for the virus and demonstrated the capability of the recombinant viruses to be introduced with desired modifications or reporter genes without any negative impacts on virus characteristics in cell culture. Recombinant viruses are also useful to evaluate antiviral efficacy. Overall, our system can be a promising tool to reveal the molecular mechanisms of the viral life cycle of feline coronavirus and disease progression of feline infectious peritonitis.

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
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.

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

Intra-individual polymorphisms in the mitochondrial COI gene of tick-killing Ixodiphagus wasps parasitizing Haemaphysalis flava ticks.
Yurie Taya; Yuto Shiraki; Samuel Kelava; Naoki Fujisawa; Yuma Ohari; Mackenzie L Kwak; Saori Baba; Hideka Numata; Gita Sadaula Pandey; Yuki Ohsugi; Yuki Katada; Shiho Niwa; Shohei Ogata; Keita Matsuno; Nariaki Nonaka; Ryo Nakao
Acta tropica, 107510, 107510, 16 Dec. 2024, [International Magazine]
English, Scientific journal, Ixodid ticks are significant vectors of pathogens affecting both humans and animals. Biological control with natural enemies represents a sustainable tool for managing ticks. However, there is a substantial lack of knowledge about the natural enemies of ticks. Wasps of the genus Ixodiphagus (Encyrtidae) are currently the only known tick-specific parasitoids. While these wasps have been sporadically recorded worldwide, their presence in Eastern Asia is poorly documented. In this study, we investigated the occurrence of Ixodiphagus wasps in field-collected ticks reared on rabbits under laboratory conditions. Ticks were collected from the Hokkaido, Hokuriku, Chugoku, Shikoku, and Kyushu regions in Japan. Out of 1,933 Haemaphysalis ticks attached to rabbits, adult wasps emerged from 15 engorged ticks. All the ticks from which wasps emerged were morphologically and molecularly identified as Haemaphysalis flava. Additionally, wasp DNA was detected in unfed H. flava nymphs using a newly designed Ixodiphagus-specific PCR assay. Among nine experimental sites in the Chugoku region, Ixodiphagus wasps were detected at three sites, with parasitism rates ranging from 1.8% to 8.1%. Finally, the mitochondrial COI genes of four wasp and two tick samples were characterized using shotgun sequencing, direct sequencing and in-fusion cloning approaches. Multiple intra-individual polymorphisms were observed in all the tested samples. Further studies are needed to investigate the relationship between Ixodiphagus wasps and Ixodid ticks. An increased understanding of these parasitoid wasps could contribute to future biological control measures against ticks.

Transboundary Movement of Yezo Virus via Ticks on Migratory Birds, Japan, 2020-2021.
Ayano Nishino; Kango Tatemoto; Keita Ishijima; Yusuke Inoue; Eun-Sil Park; Tsukasa Yamamoto; Masakatsu Taira; Yudai Kuroda; Milagros Virhuez-Mendoza; Michiko Harada; Noboru Nakamura; Gen Morimoto; Hiroki Yamaguchi; Takuma Ariizumi; Ai Takano; Hiroshi Shimoda; Keita Matsuno; Ken Maeda
Emerging infectious diseases, 30, 12, 2674, 2678, Dec. 2024, [International Magazine]
English, Scientific journal, Migratory birds carry ticks harboring various pathogens, including the zoonotic Yezo virus. In Hokkaido, Japan, we collected ticks from migratory birds during 2020-2021. Eight of 385 pools, comprising 2,534 ticks, tested positive for Yezo virus RNA, suggesting Yezo virus might be spread through the flyways of migratory birds.

Saving the Ryukyu rabbit tick Haemaphysalis pentalagi
Mackenzie L. Kwak; Yurie Taya; Mariko Suzuki; Keita Matsuno; Ryo Nakao
Oryx, 07 Nov. 2024, [Peer-reviewed]
Scientific journal

Environmental and host factors underlying tick-borne virus infection in wild animals: Investigation of the emerging Yezo virus in Hokkaido, Japan
Mebuki Ito; Miku Minamikawa; Anastasiia Kovba; Hideka Numata; Tetsuji Itoh; Takuma Ariizumi; Asako Shigeno; Yuki Katada; Shiho Niwa; Yurie Taya; Yuto Shiraki; Gita Sadaula Pandey; Nariaki Nonaka; Ryo Nakao; Ryosuke Omori; Yuma Ohari; Norikazu Isoda; Michito Shimozuru; Toshio Tsubota; Keita Matsuno; Mariko Sashika
Ticks and Tick-borne Diseases, 15, 6, 102419, 102419, Elsevier BV, Nov. 2024, [Corresponding author]
Scientific journal

Environmental and host factors underlying tick infestation in invasive raccoons (Procyon lotor) in Hokkaido, Japan
Mebuki Ito; Miku Minamikawa; Anastasiia Kovba; Hideka Numata; Tetsuji Itoh; Yuki Katada; Shiho Niwa; Yurie Taya; Yuto Shiraki; Gita Sadaula Pandey; Samuel Kelava; Nariaki Nonaka; Ryo Nakao; Ryosuke Omori; Yuma Ohari; Norikazu Isoda; Michito Shimozuru; Toshio Tsubota; Keita Matsuno; Mariko Sashika
Ticks and Tick-borne Diseases, 15, 6, 102389, 102389, Elsevier BV, Nov. 2024, [Corresponding author]
Scientific journal

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

Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariants
Hisano Yajima; Tomo Nomai; Kaho Okumura; Katsumi Maenaka; Jumpei Ito; Takao Hashiguchi; Kei Sato; Keita Matsuno; Naganori Nao; Hirofumi Sawa; Keita Mizuma; Jingshu Li; Izumi Kida; Yume Mimura; Yuma Ohari; Shinya Tanaka; Masumi Tsuda; Lei Wang; Yoshikata Oda; Zannatul Ferdous; Kenji Shishido; Hiromi Mohri; Miki Iida; Takasuke Fukuhara; Tomokazu Tamura; Rigel Suzuki; Saori Suzuki; Shuhei Tsujino; Hayato Ito; Yu Kaku; Naoko Misawa; Arnon Plianchaisuk; Ziyi Guo; Alfredo A. Hinay; Kaoru Usui; Wilaiporn Saikruang; Spyridon Lytras; Keiya Uriu; Ryo Yoshimura; Shusuke Kawakubo; Luca Nishumura; Yusuke Kosugi; Shigeru Fujita; Jarel Elgin M.Tolentino; Luo Chen; Lin Pan; Wenye Li; Maximilian Stanley Yo; Kio Horinaka; Mai Suganami; Mika Chiba; Kyoko Yasuda; Keiko Iida; Adam Patrick Strange; Naomi Ohsumi; Shiho Tanaka; Eiko Ogawa; Tsuki Fukuda; Rina Osujo; Kazuhisa Yoshimura; Kenji Sadamas; Mami Nagashima; Hiroyuki Asakura; Isao Yoshida; So Nakagawa; Kazuo Takayama; Rina Hashimoto; Sayaka Deguchi; Yukio Watanabe; Yoshitaka Nakata; Hiroki Futatsusako; Ayaka Sakamoto; Naoko Yasuhara; Tateki Suzuki; Kanako Kimura; Jiei Sasaki; Yukari Nakajima; Takashi Irie; Ryoko Kawabata; Kaori Sasaki-Tabata; Terumasa Ikeda; Hesham Nasser; Ryo Shimizu; Mst Monira Begum; Michael Jonathan; Yuka Mugita; Sharee Leong; Otowa Takahashi; Takamasa Ueno; Chihiro Motozono; Mako Toyoda; Akatsuki Saito; Anon Kosaka; Miki Kawano; Natsumi Matsubara; Tomoko Nishiuchi; Jiri Zahradnik; Prokopios Andrikopoulos; Miguel Padilla-Blanco; Aditi Konar
mBio, 15, 10, American Society for Microbiology, 16 Oct. 2024
Scientific journal, ABSTRACT

Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in the human population, controlling the COVID-19 pandemic has been challenging. Understanding how the virus enhances its fitness during a pandemic could offer valuable insights for more effective control of viral epidemics. In this manuscript, we review the evolution of SARS-CoV-2 from early 2022 to the end of 2023—from Omicron BA.2 to XBB descendants. Focusing on viral evolution during this period, we provide concrete examples that SARS-CoV-2 has increased its fitness by enhancing several functions of the spike (S) protein, including its binding affinity to the ACE2 receptor and its ability to evade humoral immunity. Furthermore, we explore how specific mutations modify these functions of the S protein through structural alterations. This review provides evolutionary, molecular, and structural insights into how SARS-CoV-2 has increased its fitness and repeatedly caused epidemic surges during the pandemic.

Elephant endotheliotropic herpesvirus gB-specific antibody levels in sera of Asian elephants (Elephas maximus) in Japanese zoos.
Kazuya Takehana; Tabitha E Hoornweg; Willem Schaftenaar; Victor Pgm Rutten; Cornelis Am de Haan; Keita Matsuno
The Journal of veterinary medical science, 16 Oct. 2024, [Last author], [Domestic magazines]
English, Scientific journal, Prevalence of elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants in Japan was assessed by determination of EEHV gB specific antibody levels. Among 28 healthy Asian (sub)adult elephants from 11 zoos, 27 animals exhibited intermediate to high antibody levels. Like elsewhere worldwide, this suggested exposure of Asian elephants in Japan to at least one EEHV (sub)species. Longitudinal observations of two elephants monitored from birth to 30-month of age showed consistent high antibody levels. Another juvenile showed antibody levels that decreased to undetectable levels prior to death at 13 months of age. This fatal case supports earlier reports that low antibody levels are a risk factor for development of EEHV hemorrhagic disease.

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

Hemagglutinin and neuraminidase of a non-pathogenic H7N7 avian influenza virus coevolved during the acquisition of intranasal pathogenicity in chickens
Takaya Ichikawa; Takahiro Hiono; Masatoshi Okamatsu; Junki Maruyama; Daiki Kobayashi; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
Archives of Virology, Oct. 2024
English, Scientific journal

Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.
Shuhei Tsujino; Sayaka Deguchi; Tomo Nomai; Miguel Padilla-Blanco; Arnon Plianchaisuk; Lei Wang; Mst Monira Begum; Keiya Uriu; Keita Mizuma; Naganori Nao; Isshu Kojima; Tomoya Tsubo; Jingshu Li; Yasufumi Matsumura; Miki Nagao; Yoshitaka Oda; Masumi Tsuda; Yuki Anraku; Shunsuke Kita; Hisano Yajima; Kaori Sasaki-Tabata; Ziyi Guo; Alfredo A Hinay Jr; Kumiko Yoshimatsu; Yuki Yamamoto; Tetsuharu Nagamoto; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Hesham Nasser; Michael Jonathan; Olivia Putri; Yoonjin Kim; Luo Chen; Rigel Suzuki; Tomokazu Tamura; Katsumi Maenaka; Takashi Irie; Keita Matsuno; Shinya Tanaka; Jumpei Ito; Terumasa Ikeda; Kazuo Takayama; Jiri Zahradnik; Takao Hashiguchi; Takasuke Fukuhara; Kei Sato
Microbiology and immunology, 68, 9, 305, 330, Sep. 2024, [International Magazine]
English, Scientific journal, In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.

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

Author Correction: Unraveling the phylogenetics of genetically closely related species, Haemaphysalis japonica and Haemaphysalis megaspinosa, using entire tick mitogenomes and microbiomes.
Mohamed Abdallah Mohamed Moustafa; Wessam M A Mohamed; Elisha Chatanga; Doaa Naguib; Keita Matsuno; Alexander W Gofton; Stephen C Barker; Nariaki Nonaka; Ryo Nakao
Scientific reports, 14, 1, 12937, 12937, 05 Jun. 2024, [International Magazine]
English

Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236.
Shigeru Fujita; Arnon Plianchaisuk; Sayaka Deguchi; Hayato Ito; Naganori Nao; Lei Wang; Hesham Nasser; Tomokazu Tamura; Izumi Kimura; Yukie Kashima; Rigel Suzuki; Saori Suzuki; Izumi Kida; Masumi Tsuda; Yoshitaka Oda; Rina Hashimoto; Yukio Watanabe; Keiya Uriu; Daichi Yamasoba; Ziyi Guo; Alfredo A Hinay Jr; Yusuke Kosugi; Luo Chen; Lin Pan; Yu Kaku; Hin Chu; Flora Donati; Sarah Temmam; Marc Eloit; Yuki Yamamoto; Tetsuharu Nagamoto; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Yutaka Suzuki; Jumpei Ito; Terumasa Ikeda; Shinya Tanaka; Keita Matsuno; Takasuke Fukuhara; Kazuo Takayama; Kei Sato
EBioMedicine, 104, 105181, 105181, Jun. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).

Unraveling the phylogenetics of genetically closely related species, Haemaphysalis japonica and Haemaphysalis megaspinosa, using entire tick mitogenomes and microbiomes.
Mohamed Abdallah Mohamed Moustafa; Wessam M A Mohamed; Elisha Chatanga; Doaa Nagib; Keita Matsuno; Alexander W Gofton; Stephen C Barker; Nariaki Nonaka; Ryo Nakao
Scientific reports, 14, 1, 9961, 9961, 30 Apr. 2024, [International Magazine]
English, Scientific journal, Ticks have a profound impact on public health. Haemaphysalis is one of the most widespread genera in Asia, including Japan. The taxonomy and genetic differentiation of Haemaphysalis spp. is challenging. For instance, previous studies struggled to distinguish Haemaphysalis japonica and Haemaphysalis megaspinosa due to the dearth of nucleotide sequence polymorphisms in widely used barcoding genes. The classification of H. japonica japonica and its related sub-species Haemaphysalis japonica douglasi or Haemaphysalis jezoensis is also confused due to their high morphological similarity and a lack of molecular data that support the current classification. We used mitogenomes and microbiomes of H. japonica and H. megaspinosa to gain deeper insights into the phylogenetic relationships and genetic divergence between two species. Phylogenetic analyses of concatenated nucleotide sequences of protein-coding genes and ribosomal DNA genes distinguished H. japonica and H. megaspinosa as monophyletic clades, with further subdivision within the H. japonica clade. The 16S rRNA and NAD5 genes were valuable markers for distinguishing H. japonica and H. megaspinosa. Population genetic structure analyses indicated that genetic variation within populations accounted for a large proportion of the total variation compared to variation between populations. Microbiome analyses revealed differences in alpha and beta diversity between H. japonica and H. megaspinosa: H. japonica had the higher diversity. Coxiella sp., a likely endosymbiont, was found in both Haemaphysalis species. The abundance profiles of likely endosymbionts, pathogens, and commensals differed between H. japonica and H. megaspinosa: H. megaspinosa was more diverse.

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

Virological characteristics of the SARS-CoV-2 BA.2.86 variant.
Tomokazu Tamura; Keita Mizuma; Hesham Nasser; Sayaka Deguchi; Miguel Padilla-Blanco; Yoshitaka Oda; Keiya Uriu; Jarel E M Tolentino; Shuhei Tsujino; Rigel Suzuki; Isshu Kojima; Naganori Nao; Ryo Shimizu; Lei Wang; Masumi Tsuda; Michael Jonathan; Yusuke Kosugi; Ziyi Guo; Alfredo A Hinay Jr; Olivia Putri; Yoonjin Kim; Yuri L Tanaka; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Akatsuki Saito; Jumpei Ito; Takashi Irie; Shinya Tanaka; Jiri Zahradnik; Terumasa Ikeda; Kazuo Takayama; Keita Matsuno; Takasuke Fukuhara; Kei Sato
Cell host & microbe, 32, 2, 170, 180, 14 Feb. 2024, [International Magazine]
English, Scientific journal, In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct SARS-CoV-2 lineage, the BA.2.86 variant, also emerged. BA.2.86 is phylogenetically distinct from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Additionally, four clinically available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 are significantly lower than those of BA.2 both in vitro and in vivo, the attenuated pathogenicity of BA.2.86 is likely due to its decreased replication capacity. These findings uncover the features of BA.2.86, providing insights for control and treatment.

The impact of PA/I38 substitutions and PA polymorphisms on the susceptibility of zoonotic influenza A viruses to baloxavir.
Keiichi Taniguchi; Takeshi Noshi; Shinya Omoto; Akihiko Sato; Takao Shishido; Keita Matsuno; Masatoshi Okamatsu; Scott Krauss; Richard J Webby; Yoshihiro Sakoda; Hiroshi Kida
Archives of virology, 169, 2, 29, 29, 12 Jan. 2024, [International Magazine]
English, Scientific journal, Genetic reassortment of avian, swine, and human influenza A viruses (IAVs) poses potential pandemic risks. Surveillance is important for influenza pandemic preparedness, but the susceptibility of zoonotic IAVs to the cap-dependent endonuclease inhibitor baloxavir acid (BXA) has not been thoroughly researched. Although an amino acid substitution at position 38 in the polymerase acidic protein (PA/I38) in seasonal IAVs reduces BXA susceptibility, PA polymorphisms at position 38 are rarely seen in zoonotic IAVs. Here, we examined the impact of PA/I38 substitutions on the BXA susceptibility of recombinant A(H5N1) viruses. PA mutants that harbored I38T, F, and M were 48.2-, 24.0-, and 15.5-fold less susceptible, respectively, to BXA than wild-type A(H5N1) but were susceptible to the neuraminidase inhibitor oseltamivir acid and the RNA polymerase inhibitor favipiravir. PA mutants exhibited significantly impaired replicative fitness in Madin-Darby canine kidney cells at 24 h postinfection. In addition, in order to investigate new genetic markers for BXA susceptibility, we screened geographically and temporally distinct IAVs isolated worldwide from birds and pigs. The results showed that BXA exhibited antiviral activity against avian and swine viruses with similar levels to seasonal isolates. All viruses tested in the study lacked the PA/I38 substitution and were susceptible to BXA. Isolates harboring amino acid polymorphisms at positions 20, 24, and 37, which have been implicated in the binding of BXA to the PA endonuclease domain, were also susceptible to BXA. These results suggest that monitoring of the PA/I38 substitution in animal-derived influenza viruses is important for preparedness against zoonotic influenza virus outbreaks.

No Evidence of SARS‐CoV‐2 Infection in Urban Wildlife of Hokkaido, Japan
Anastasiia Kovba; Naganori Nao; Michito Shimozuru; Mariko Sashika; Chihiro Takahata; Kei Sato; Keiya Uriu; Masami Yamanaka; Masanao Nakanishi; Genta Ito; Mebuki Ito; Miku Minamikawa; Kotaro Shimizu; Koichi Goka; Manabu Onuma; Keita Matsuno; Toshio Tsubota
Transboundary and Emerging Diseases, 2024, 1, Wiley, Jan. 2024, [Corresponding author]
Scientific journal, Various domestic and wildlife species have been found susceptible to and infected with SARS‐CoV‐2, the causative agent of COVID‐19, around the globe, raising concerns about virus adaptation and transmission to new animal hosts. The virus circulation in the white‐tailed deer population in North America has further called to action for virus surveillance in the wildlife. Here, we report on the first SARS‐CoV‐2 survey of wild animals in Japan, where frequent wildlife invasions of urban areas have occurred due to the limited predation, field abandonment, the increase of human acclimatization. Genetic testing using nasal swabs and serological screening have been conducted for sika deer, brown bears, raccoons, and raccoon dogs captured in Hokkaido prefecture from the end of the Delta variant wave to the spread of the Omicron variant, between March 2022 and February 2023. No viral RNA was detected in raccoons (0/184), sika deer (0/107), and brown bears (0/14) indicating that the virus was unlikely to spread within the population of these animal species. Among 171 raccoons, 20 raccoon dogs, 100 sika deer, and 13 brown bears, one raccoon, one brown bear, and two deer tested positive in the antibodies screening with multispecies SARS‐CoV‐2 N‐protein ELISA. Still, ELISA‐positive samples tested negative in three other serological tests, emphasizing the importance of confirming serological screening results. Our results suggested that SARS‐CoV‐2 was unlikely to spillback from humans to wildlife in Hokkaido during the study period, with the emergence of new variants, continuous surveillance is of utmost importance.

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

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

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

IMPORTANCE

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

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

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

Investigation of vertical and horizontal transmission of Spiroplasma in ticks under laboratory conditions
Shohei Ogata; Rika Umemiya-Shirafuji; Kodai Kusakisako; Keita Kakisaka; Elisha Chatanga; Naoki Hayashi; Yurie Taya; Yuma Ohari; Gita Sadaula Pandey; Abdelbaset Eweda Abdelbaset; Yongjin Qiu; Keita Matsuno; Nariaki Nonaka; Ryo Nakao
Scientific Reports, 13, 1, 13265, 13265, Springer Science and Business Media LLC, 15 Aug. 2023, [International Magazine]
English, Scientific journal, Abstract

Many arthropods harbour bacterial symbionts, which are maintained by vertical and/or horizontal transmission. Spiroplasma is one of the most well-known symbionts of ticks and other arthropods. It is still unclear how Spiroplasma infections have spread in tick populations despite its high prevalence in some tick species. In this study, Ixodes ovatus, which has been reported to harbour Spiroplasma ixodetis at high frequencies, was examined for its vertical transmission potential under experimental conditions. Next, two isolates of tick-derived Spiroplasma, S. ixodetis and Spiroplasma mirum, were experimentally inoculated into Spiroplasma-free Haemaphysalis longicornis colonies and the presence of Spiroplasma in their eggs and larvae was tested. Our experimental data confirmed that S. ixodetis was transmitted to eggs and larvae in a vertical manner in the original host I. ovatus. In the second experiment, there was no significant difference in engorged weight, egg weight, and hatching rate between Spiroplasma-inoculated and control H. longicornis groups. This suggested that Spiroplasma infection does not affect tick reproduction. Spiroplasma DNA was only detected in the eggs and larvae derived from some individuals of S. ixodetis-inoculated groups. This has demonstrated the potential of horizontal transmission between different tick species. These findings may help understand the transmission dynamics of Spiroplasma in nature and its adaptation mechanism to host arthropod species.

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, [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.

ダニ媒介感染症の最近の話題 エゾウイルス発見の経緯
松野 啓太; 児玉 文宏; 山口 宏樹; 有泉 拓馬; 前田 健; 西條 政幸; 川端 寛樹
日本化学療法学会雑誌, 71, 4, 411, 411, (公社)日本化学療法学会, Jul. 2023
Japanese

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

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, [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, [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.

Direct detection of elephant endotheliotropic herpesvirus 1 (EEHV1) DNA in heparinized plasma by loop-mediated isothermal amplification.
Kazuya Takehana; Keita Matsuno
The Journal of veterinary medical science, 85, 4, 459, 462, 30 Mar. 2023, [Last author], [Domestic magazines]
English, Scientific journal, Elephant endotheliotropic herpesvirus (EEHV) causes a fatal hemorrhagic disease and is a significant cause of mortality in juvenile Asian elephants. A loop-mediated isothermal amplification (LAMP) method was developed to rapidly diagnose EEHV viremia. However, extracting DNA from whole blood samples to perform LAMP hampers diagnosis in a field setting. Here, we established the Direct-LAMP method, using heparinized plasma without extracting the DNA to speed up and simplify the test. EEHV-positive specimens were tested using the Direct-LAMP. The detection limit was calculated to be 101.3 copies/μL using the mimetic samples, which was almost identical to the value determined in LAMP in which DNA was extracted. Hence, the Direct-LAMP provided a more rapid diagnosis to save, which could prevent elephant deaths.

ダニ媒介感染症の最近の話題 エゾウイルス発見の経緯
松野 啓太; 児玉 文宏; 山口 宏樹; 有泉 拓馬; 前田 健; 西條 政幸; 川端 寛樹
日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集, 97回・71回, シンポジウム7, シンポジウム7, 日本感染症学会・日本化学療法学会, Mar. 2023
Japanese

渡り鳥によるYezoウイルス保有マダニの運搬
西野 綾乃; 立本 完吾; 井上 雄介; 石嶋 慧多; 黒田 雄大; Mendoza Milagros; 原田 倫子; 朴 ウンシル; 下田 宙; 高野 愛; 仲村 昇; 森本 元; 松野 啓太; 前田 健
衛生動物, 74, Suppl., 61, 61, 日本衛生動物学会, Mar. 2023
Japanese

渡り鳥によるYezoウイルス保有マダニの運搬
西野 綾乃; 立本 完吾; 井上 雄介; 石嶋 慧多; 黒田 雄大; Mendoza Milagros; 原田 倫子; 朴 ウンシル; 下田 宙; 高野 愛; 仲村 昇; 森本 元; 松野 啓太; 前田 健
衛生動物, 74, Suppl., 61, 61, 日本衛生動物学会, Mar. 2023
Japanese

Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication.
Yuta Tsukamoto; Takahiro Hiono; Shintaro Yamada; Keita Matsuno; Aileen Faist; Tobias Claff; Jianyu Hou; Vigneshwaran Namasivayam; Anja Vom Hemdt; Satoko Sugimoto; Jin Ying Ng; Maria H Christensen; Yonas M Tesfamariam; Steven Wolter; Stefan Juranek; Thomas Zillinger; Stefan Bauer; Takatsugu Hirokawa; Florian I Schmidt; Georg Kochs; Masayuki Shimojima; Yi-Shuian Huang; Andreas Pichlmair; Beate M Kümmerer; Yoshihiro Sakoda; Martin Schlee; Linda Brunotte; Christa E Müller; Manabu Igarashi; Hiroki Kato
Science (New York, N.Y.), 379, 6632, 586, 591, 10 Feb. 2023, [International Magazine]
English, Scientific journal, Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification of the cap portion by host 2'-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from Streptomyces, called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket to restrict influenza virus replication. Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lung explants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.

国内のネコ・イヌにおける重症熱性血小板減少症候群の発生状況
石嶋 慧多; 平良 雅克; 松鵜 彩; 朴 ウンシル; 立本 完吾; 木村 昌伸; 藤田 修; 前田 健; 森川 茂; 岡林 環樹; 早坂 大輔; 井上 真吾; 高松 由基; 桃井 康行; 水谷 哲也; 松野 啓太; 山岡 弘二
病原微生物検出情報月報, 44, 2, 31, 32, 国立感染症研究所, Feb. 2023
Japanese

国内のネコ・イヌにおける重症熱性血小板減少症候群の発生状況
石嶋 慧多; 平良 雅克; 松鵜 彩; 朴 ウンシル; 立本 完吾; 木村 昌伸; 藤田 修; 前田 健; 森川 茂; 岡林 環樹; 早坂 大輔; 井上 真吾; 高松 由基; 桃井 康行; 水谷 哲也; 松野 啓太; 山岡 弘二
病原微生物検出情報月報, 44, 2, 31, 32, 国立感染症研究所, Feb. 2023
Japanese

Genetic, Antigenic, and Pathobiological Characterization of H9 and H6 Low Pathogenicity Avian Influenza Viruses Isolated in Vietnam from 2014 to 2018.
Kien Trung Le; Lam Thanh Nguyen; Loc Tan Huynh; Duc-Huy Chu; Long Van Nguyen; Tien Ngoc Nguyen; Tien Ngoc Tien; Keita Matsuno; Masatoshi Okamatsu; Takahiro Hiono; Norikazu Isoda; Yoshihiro Sakoda
Microorganisms, 11, 2, 18 Jan. 2023, [International Magazine]
English, Scientific journal, The H9 and H6 subtypes of low pathogenicity avian influenza viruses (LPAIVs) cause substantial economic losses in poultry worldwide, including Vietnam. Herein, we characterized Vietnamese H9 and H6 LPAIVs to facilitate the control of avian influenza. The space-time representative viruses of each subtype were selected based on active surveillance from 2014 to 2018 in Vietnam. Phylogenetic analysis using hemagglutinin genes revealed that 54 H9 and 48 H6 Vietnamese LPAIVs were classified into the sublineages Y280/BJ94 and Group II, respectively. Gene constellation analysis indicated that 6 and 19 genotypes of the H9 and H6 subtypes, respectively, belonged to the representative viruses. The Vietnamese viruses are genetically related to the previous isolates and those in neighboring countries, indicating their circulation in poultry after being introduced into Vietnam. The antigenicity of these subtypes was different from that of viruses isolated from wild birds. Antigenicity was more conserved in the H9 viruses than in the H6 viruses. Furthermore, a representative H9 LPAIV exhibited systemic replication in chickens, which was enhanced by coinfection with avian pathogenic Escherichia coli O2. Although H9 and H6 were classified as LPAIVs, their characterization indicated that their silent spread might significantly affect the poultry industry.

Virological, pathological, and glycovirological investigations of an Ezo red fox and a tanuki naturally infected with H5N1 highly pathogenic avian influenza viruses in Hokkaido, Japan
Takahiro Hiono; Daiki Kobayashi; Atsushi Kobayashi; Tamami Suzuki; Yuki Satake; Rio Harada; Keita Matsuno; Mariko Sashika; Hinako Ban; Maya Kobayashi; Keisuke Aoshima; Fumihito Takaya; Hiroko Fujita; Norikazu Isoda; Takashi Kimura; Yoshihiro Sakoda
Virology, 578, 35, 44, Jan. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, In winter/spring 2021-2022, high pathogenicity avian influenza viruses (HPAIVs) that are genetically closely related to each other were detected worldwide. In a public garden in Sapporo, Hokkaido, Japan, a crow die-off by HPAIV infection occurred from March 29 to May 18, 2022. During the event, H5N1 HPAIVs were isolated from an Ezo red fox (Vulpes vulpes schrencki) and a tanuki (Nyctereutes procyonoides albus) found in the same garden. The fox showed viral meningoencephalitis and moderate virus replication in the upper respiratory tract, whereas the tanuki showed viral conjunctivitis and secondary bacterial infection in the eyes accompanied with visceral larva migrans. Viruses isolated from the fox and the tanuki were genetically closely related to those isolated from crows in the same garden. Various α2-3 sialosides were found in the respiratory tracts of these canid mammals, consistent with HPAIV infections in these animals. This study highlighted the importance of monitoring HPAIV infections in wild carnivore mammals to detect the potential virus spreading in nature.

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

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

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

キタキツネ及びタヌキからの高病原性鳥インフルエンザウイルスの分離
日尾野 隆大; 磯田 典和; 小林 篤史; 小林 大樹; 鈴木 玲海; 佐竹 優樹; 松野 啓太; 佐鹿 万里子; 伴 日向子; 小林 茉弥; 高谷 文仁; 冨士田 裕子; 木村 享史; 迫田 義博
日本獣医学会学術集会講演要旨集, 165回, [DV1A, 09], (公社)日本獣医学会, Sep. 2022
Japanese

高病原性鳥インフルエンザウイルスに感染したキタキツネの病理学的解析とウイルス受容体の検出
小林 大樹; 小林 篤史; 日尾野 隆大; 原田 里桜; 鈴木 玲海; 松野 啓太; 磯田 典和; 高谷 文仁; 冨士田 裕子; 木村 享史; 迫田 義博
日本獣医学会学術集会講演要旨集, 165回, [DV1A, 10], (公社)日本獣医学会, Sep. 2022
Japanese

渡り鳥から採集したマダニ中のYezoウイルス遺伝子解析
西野 綾乃; 立本 完吾; 井上 雄介; 石嶋 慧多; 黒田 雄大; Mendoza Milagros Virhuez; 原田 倫子; 朴 ウンシル; 下田 宙; 高野 愛; 仲村 昇; 森本 元; 松野 啓太; 前田 健
日本獣医学会学術集会講演要旨集, 165回, [DV2A, 09], (公社)日本獣医学会, Sep. 2022
Japanese

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; M.S.T. 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, Elsevier BV, Sep. 2022, [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.

Comparative mitogenomics elucidates the population genetic structure of Amblyomma testudinarium in Japan and a closely related Amblyomma species in Myanmar
Wessam Mohamed Ahmed Mohamed; Mohamed Abdallah Mohamed Moustafa; May June Thu; Keita Kakisaka; Elisha Chatanga; Shohei Ogata; Naoki Hayashi; Yurie Taya; Yuma Ohari; Doaa Naguib; Yongjin Qiu; Keita Matsuno; Saw Bawm; Lat Lat Htun; Stephen C. Barker; Ken Katakura; Kimihito Ito; Nariaki Nonaka; Ryo Nakao
Evolutionary Applications, 15, 7, 1062, 1078, Wiley, 23 Jun. 2022, [International Magazine]
English, Scientific journal, Ticks are the second most important vector capable of transmitting diseases affecting the health of both humans and animals. Amblyomma testudinarium Koch 1844 (Acari: Ixodidae), is a hard tick species having a wide geographic distribution in Asia. In this study, we analyzed the composition of A. testudinarium whole mitogenomes from various geographical regions in Japan and investigated the population structure, demographic patterns, and phylogeographic relationship with other ixodid species. In addition, we characterized a potentially novel tick species closely related to A. testudinarium from Myanmar. Phylogeographic inference and evolutionary dynamics based on the 15 mitochondrial coding genes supported that A. testudinarium population in Japan is resolved into a star-like haplogroup and suggested a distinct population structure of A. testudinarium from Amami island in Kyushu region. Correlation analysis using Mantel test statistics showed that no significant correlation was observed between the genetic and geographic distances calculated between the A. testudinarium population from different localities in Japan. Finally, demographic analyses, including mismatch analysis and Tajima's D test, suggested a possibility of recent population expansion occurred within Japanese haplogroup after a bottleneck event. Although A. testudinarium has been considered widespread and common in East and Southeast Asia, the current study suggested that potentially several cryptic Amblyomma spp. closely related to A. testudinarium are present in Asia.

Risk profile of low pathogenicity avian influenza virus infections in farms in southern Vietnam.
Kien Trung LE; Norikazu Isoda; Lam Thanh Nguyen; Duc-Huy Chu; Long Van Nguyen; Minh Quang Phan; Diep Thi Nguyen; Tien Ngoc Nguyen; Tien Ngoc Tien; Tung Thanh LE; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda
The Journal of veterinary medical science, 84, 6, 860, 868, 13 May 2022, [Domestic magazines]
English, Scientific journal, The impact of low pathogenicity avian influenza (LPAI) has been confirmed mainly in farms. Unlike apparent losses caused by the high pathogenicity avian influenza (HPAI), the LPAI impact has been hardly evaluated due to underestimating its spread and damage. In 2019, a questionnaire study was conducted in southern Vietnam to identify the specific risk factors of LPAI virus (LPAIV) circulation and to find associations between husbandry activities and LPAI prevalence. A multilevel regression analysis indicated that keeping Muscovy ducks during farming contributed to LPAIV positivity [Odds ratio=208.2 (95% confidence interval: 13.4-1.1×104)]. In cluster analysis, farmers willing to report avian influenza (AI) events and who agreed with the local AI control policy had a slightly lower risk for LPAIV infection although there was no significance in the correlation between farmer characteristics and LPAI occurrence. These findings indicated that keeping Muscovy ducks without appropriate countermeasures might increase the risk of LPAIV infection. Furthermore, specific control measures at the local level are effective for LPAIV circulation, and the improvement of knowledge about biosecurity and attitude contributes to reducing LPAI damage.

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, 02 May 2022, [International Magazine]
English, Scientific journal, Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.

Novel symbionts and potential human pathogens excavated from argasid tick microbiomes that are shaped by dual or single symbiosis.
Mohamed Abdallah Mohamed Moustafa; Wessam Mohamed Ahmed Mohamed; Alice C C Lau; Elisha Chatanga; Yongjin Qiu; Naoki Hayashi; Doaa Naguib; Kozue Sato; Ai Takano; Keita Matsuno; Nariaki Nonaka; DeMar Taylor; Hiroki Kawabata; Ryo Nakao
Computational and structural biotechnology journal, 20, 1979, 1992, Apr. 2022, [International Magazine]
English, Scientific journal, Research on vector-associated microbiomes has been expanding due to increasing emergence of vector-borne pathogens and awareness of the importance of symbionts in the vector physiology. However, little is known about microbiomes of argasid (or soft-bodied) ticks due to limited access to specimens. We collected four argasid species (Argas japonicus, Carios vespertilionis, Ornithodoros capensis, and Ornithodoros sawaii) from the nests or burrows of their vertebrate hosts. One laboratory-reared argasid species (Ornithodoros moubata) was also included. Attempts were then made to isolate and characterize potential symbionts/pathogens using arthropod cell lines. Microbial community structure was distinct for each tick species. Coxiella was detected as the predominant symbiont in four tick species where dual symbiosis between Coxiella and Rickettsia or Coxiella and Francisella was observed in C. vespertilionis and O. moubata, respectively. Of note, A. japonicus lacked Coxiella and instead had Occidentia massiliensis and Thiotrichales as alternative symbionts. Our study found strong correlation between tick species and life stage. We successfully isolated Oc. massiliensis and characterized potential pathogens of genera Ehrlichia and Borrelia. The results suggest that there is no consistent trend of microbiomes in relation to tick life stage that fit all tick species and that the final interpretation should be related to the balance between environmental bacterial exposure and endosymbiont ecology. Nevertheless, our findings provide insights on the ecology of tick microbiomes and basis for future investigations on the capacity of argasid ticks to carry novel pathogens with public health importance.

Clinical review of Elephant endotheliotropic herpes virus （EEHV） associated disease in Asian elephants （<i>Elephas maximus</i>）
Kazuya TAKEHANA; Shigehisa KAWAKAMI; Chatchote Thitaram; Keita MATSUNO
Japanese Journal of Zoo and Wildlife Medicine, 27, 1, 17, 27, Japanese Society of Zoo and Wildlife Medicine, 01 Mar. 2022
Scientific journal

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, 01 Feb. 2022, [International Magazine]
English, Scientific journal, The emergence of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, is an urgent global health concern (ref.1). Our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments show that Omicron is less fusogenic than Delta and an ancestral SARS-CoV-2 strain. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell-cell fusion2,3, Omicron S is less efficiently cleaved compared to Delta S and ancestral SARS-CoV-2 S. Furthermore, in a hamster model, Omicron shows decreased lung infectivity and is less pathogenic compared to Delta and ancestral SARS-CoV-2.

N-glycolylneuraminic acid binding of avian and equine H7 influenza A viruses.
Cindy M Spruit; Xueyong Zhu; Ilhan Tomris; María Ríos Carrasco; Alvin X Han; Frederik Broszeit; Roosmarijn van der Woude; Kim M Bouwman; Michel M T Luu; Keita Matsuno; Yoshihiro Sakoda; Colin A Russell; Ian A Wilson; Geert-Jan Boons; Robert P de Vries
Journal of virology, 96, 5, e02120-21, 19 Jan. 2022, [International Magazine]
English, Scientific journal, Influenza A viruses (IAV) initiate infection by binding to glycans with terminal sialic acids on the cell surface. Hosts of IAV variably express two major forms of sialic acid, N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc). NeuGc is produced in most mammals including horses and pigs, but is absent in humans, ferrets, and birds. The only known naturally occurring IAVs that exclusively bind NeuGc are extinct highly pathogenic equine H7N7 viruses. We determined the crystal structure of a representative equine H7 hemagglutinin (HA) in complex with NeuGc and observed high similarity in the receptor-binding domain with an avian H7 HA. To determine the molecular basis for NeuAc and NeuGc specificity, we performed systematic mutational analyses, based on the structural insights, on two distant avian H7 HAs and an H15 HA. We found that mutation A135E is key for binding α2,3-linked NeuGc but does not abolish NeuAc binding. Additional mutations S128T, I130V, T189A, and K193R converted the specificity from NeuAc to NeuGc. We investigated the residues at positions 128, 130, 135, 189, and 193 in a phylogenetic analysis of avian and equine H7 HAs. This revealed a clear distinction between equine and avian residues. The highest variability was observed at key position 135, of which only the equine glutamic acid led to NeuGc binding. These results demonstrate that genetically distinct H7 and H15 HAs can be switched from NeuAc to NeuGc binding and vice versa after introduction of several mutations, providing insights into the adaptation of H7 viruses to NeuGc receptors. (250 words) Importance Influenza A viruses cause millions of cases of severe illness and deaths annually. To initiate infection and replicate, the virus first needs to bind to a structure on the cell surface, like a key fitting in a lock. For influenza A viruses, these 'keys' (receptors) on the cell surface are chains of sugar molecules (glycans). The terminal sugar on these glycans is often either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc). Most influenza A viruses bind NeuAc, but a small minority binds NeuGc. NeuGc is present in species like horses, pigs, and mice, but not in humans, ferrets, and birds. Here, we investigated the molecular determinants of NeuGc specificity and the origin of viruses that bind NeuGc.

Characterization of the In Vitro and In Vivo Efficacy of Baloxavir Marboxil against H5 Highly Pathogenic Avian Influenza Virus Infection.
Keiichi Taniguchi; Yoshinori Ando; Masanori Kobayashi; Shinsuke Toba; Haruaki Nobori; Takao Sanaki; Takeshi Noshi; Makoto Kawai; Ryu Yoshida; Akihiko Sato; Takao Shishido; Akira Naito; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
Viruses, 14, 1, 111, 08 Jan. 2022, [International Magazine]
English, Scientific journal, Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-h delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Dynamics of invasion and dissemination of H5N6 highly pathogenic avian influenza viruses in 2016-2017 winter in Japan.
Kosuke Soda; Hiroichi Ozaki; Hiroshi Ito; Tatsufumi Usui; Masatoshi Okamatsu; Keita Matsuno; Yoshihiro Sakoda; Tsuyoshi Yamaguchi; Toshihiro Ito
The Journal of veterinary medical science, 83, 12, 1891, 1898, 02 Dec. 2021, [Domestic magazines]
English, Scientific journal, Large highly pathogenic avian influenza (HPAI) outbreaks caused by clade 2.3.4.4e H5N6 viruses occurred in Japan during the 2016-2017 winter. To date, several reports regarding these outbreaks have been published, however a comprehensive study including geographical and time course validations has not been performed. Herein, 58 Japanese HPAI virus (HPAIV) isolates from the 2016-2017 season were added for phylogenetic analyses and the antigenic relationships among the causal viruses were elucidated. The locations where HPAIVs were found in the early phase of the outbreaks were clustered into three regions. Genotypes C1, C5, and C6-8 HPAIVs were found in specific areas. Two strains had phylogenetically distinct hemagglutinin (HA) and non-structural (NS) genes from other previously identified strains, respectively. The estimated latest divergence date between the viral genotypes suggests that genetic reassortment occurred in bird populations before their winter migration to Japan. Antigenic differences in 2016-2017 HPAIVs were not observed, suggesting that antibody pressure in the birds did not contribute to the selection of HPAIV genotypes. In the late phase, the majority of HPAI cases in wild birds occurred south of the lake freezing line. At the end of the outbreak, HPAI re-occurred in East coast region, which may be due to the spring migration route of Anas bird species. These trends were similar to those observed in the 2010-2011 outbreaks, suggesting there is a typical pattern of seeding and dissemination of HPAIV in Japan.

Functional Importance of Hydrophobic Patches on the Ebola Virus VP35 IFN-Inhibitory Domain.
Nodoka Kasajima; Keita Matsuno; Hiroko Miyamoto; Masahiro Kajihara; Manabu Igarashi; Ayato Takada
Viruses, 13, 11, 2316, 20 Nov. 2021, [International Magazine]
English, Scientific journal, Viral protein 35 (VP35) of Ebola virus (EBOV) is a multifunctional protein that mainly acts as a viral polymerase cofactor and an interferon antagonist. VP35 interacts with the viral nucleoprotein (NP) and double-stranded RNA for viral RNA transcription/replication and inhibition of type I interferon (IFN) production, respectively. The C-terminal portion of VP35, which is termed the IFN-inhibitory domain (IID), is important for both functions. To further identify critical regions in this domain, we analyzed the physical properties of the surface of VP35 IID, focusing on hydrophobic patches, which are expected to be functional sites that are involved in interactions with other molecules. Based on the known structural information of VP35 IID, three hydrophobic patches were identified on its surface and their biological importance was investigated using minigenome and IFN-β promoter-reporter assays. Site-directed mutagenesis revealed that some of the amino acid substitutions that were predicted to disrupt the hydrophobicity of the patches significantly decreased the efficiency of viral genome replication/transcription due to reduced interaction with NP, suggesting that the hydrophobic patches might be critical for the formation of a replication complex through the interaction with NP. It was also found that the hydrophobic patches were involved in the IFN-inhibitory function of VP35. These results highlight the importance of hydrophobic patches on the surface of EBOV VP35 IID and also indicate that patch analysis is useful for the identification of amino acid residues that directly contribute to protein functions.

A systematic approach to illuminate a new hot spot of avian influenza virus circulation in South Vietnam, 2016-2017.
Kien Trung Le; Mark A Stevenson; Norikazu Isoda; Lam Thanh Nguyen; Duc-Huy Chu; Tien Ngoc Nguyen; Long Van Nguyen; Tien Ngoc Tien; Tung Thanh Le; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda
Transboundary and emerging diseases, 1, 14, 04 Nov. 2021, [International Magazine]
English, Scientific journal, In South Vietnam, live bird markets (LBMs) are key in the value chain of poultry products and spread of avian influenza virus (AIV) although they may not be the sole determinant of AIV prevalence. For this reason, a risk analysis of AIV prevalence was conducted accounting for all value chain factors. A cross-sectional study of poultry flock managers and poultry on backyard farms, commercial (high biosecurity) farms, LBMs and poultry delivery stations (PDSs) in four districts of Vinh Long province was conducted between December 2016 and August 2017. A total of 3597 swab samples were collected from birds from 101 backyard farms, 50 commercial farms, 58 sellers in LBMs and 19 traders in PDSs. Swab samples were submitted for AIV isolation. At the same time a questionnaire was administered to flock managers asking them to provide details of their knowledge, attitude and practices related to avian influenza. Multiple correspondence analysis and a mixed-effects multivariable logistic regression model were developed to identify enterprise and flock manager characteristics that increased the risk of AIV positivity. A total of 274 birds were positive for AIV isolation, returning an estimated true prevalence of 7.6% [95% confidence interval (CI): 6.8%-8.5%]. The odds of a bird being AIV positive if it was from an LBM or PDS were 45 (95% CI: 3.4-590) and 25 (95% CI: 1.4-460), respectively, times higher to the odds of a bird from a commercial poultry farm being AIV positive. The odds of birds being AIV positive for respondents with a mixed (uncertain or inconsistent) level and a low level of knowledge about AI were 5.0 (95% CI: 0.20-130) and 3.5 (95% CI: 0.2-62), respectively, times higher to the odd of birds being positive for respondents with a good knowledge of AI. LBMs and PDSs should receive specific emphasis in AI control programs in Vietnam. Our findings provide evidence to support the hypothesis that incomplete respondent knowledge of AI and AIV spread mechanism were associated with an increased risk of AIV positivity. Delivery of education programs specifically designed for those in each enterprise will assist in this regard. The timing and frequency of delivery of education programs are likely to be important if the turnover of those working in LBMs and PDSs is high.

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 Amanda 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, 02 Oct. 2021, [International Magazine]
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.

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

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

Reconstruction of mitochondrial genomes from raw sequencing data provides insights on the phylogeny of Ixodes ticks but suggests the caution for species misidentification
Wessam Mohamed Ahmed Mohamed; Mohamed Abdallah Mohamed Moustafa; Samuel Kelava; Dayana Barker; Keita Matsuno; Nariaki Nonaka; Renfu Shao; Ben J. Mans; Stephen C. Barker; Ryo Nakao
Ticks and Tick-borne Diseases, 13, 1, 101832, 101832, Elsevier BV, Sep. 2021, [International Magazine]
English, Scientific journal, High-throughput sequencing (HTS) technology has profoundly been involved in sequencing whole genomes of several organisms in a fast and cost-effective manner. Although HTS provides an alternative biomonitoring method to the time-consuming and taxonomy-expertise dependent morphological approach, still we cannot rule out the possibility of the impediment and misidentification biases. In this article we aim to retrieve whole mitochondrial genome (mitogenome) sequences from publicly available raw sequencing data for phylogenetic comparison of Ixodes persulcatus. For this comparison, we sequenced whole mitogenomes of four I. persulcatus ticks from Japan and constructed mitogenomes from raw sequencing data of 74 I. persulcatus ticks from China. Bayesian phylogenetic trees were inferred by the concatenated fifteen mitochondrial genes. We further tested our results by the phylogenetic analysis of cytochrome c oxidase subunit 1 (cox1) gene and internal transcribed spacer 2 (ITS2) sequences. Our findings showed that 70 constructed mitogenomes from China were clustered with the sequenced four mitogenomes of I. persulcatus from Japan. We also revealed that mitogenome sequences retrieved from two data sets CRR142297 and CRR142298 were clustered with Ixodes nipponensis. Moreover, other two mitogenome sequences from CRR142310 and CRR142311 formed a clade with Ixodes pavlovskyi. The phylogenetic analysis of cox1 gene and ITS2 sequences confirmed the identification errors of these four samples. The overall phylogenetics in our study concluded that accurate morphological identification is necessary before implementing HTS to avoid any misidentification biases.

Nuclear (18S-28S rRNA) and mitochondrial genome markers of Carios (Carios) vespertilionis (Argasidae) support Carios Latreille, 1796 as a lineage embedded in the Ornithodorinae: re-classification of the Carios sensu Klompen and Oliver (1993) clade into its respective subgenera.
Ben J Mans; Samuel Kelava; Ronel Pienaar; Jonathan Featherston; Minique H de Castro; Juan Quetglas; Will K Reeves; Lance A Durden; Myrna M Miller; Theresa M Laverty; Renfu Shao; Ai Takano; Hiroki Kawabata; Mohamed Abdallah Mohamed Moustafa; Ryo Nakao; Keita Matsuno; Telleasha L Greay; Kimberly L Evasco; Dayana Barker; Stephen C Barker
Ticks and tick-borne diseases, 12, 4, 101688, 101688, Jul. 2021, [International Magazine]
English, Scientific journal, Argasid systematics remains controversial with widespread adherence to the Hoogstraal (1985) classification scheme, even though it does not reflect evolutionary relationships and results in paraphyly for the main genera of soft ticks (Argasidae), namely Argas and Ornithodoros. The alternative classification scheme, proposed by Klompen and Oliver (1993), has problems of its own: most notably paraphyly of the subgenus Pavlovskyella and the controversial grouping together of the subgenera Alectorobius, Antricola, Carios, Chiropterargas, Nothoaspis, Parantricola, Reticulinasus and Subparmatus into the genus Carios. Recent phylogenetic analyses of 18S/28S rRNA sequences and mitochondrial genomes agree with the scheme of Klompen and Oliver (1993), with regard to the paraphyly of Pavlovskyella, placement of Alveonasus, Ogadenus, Proknekalia and Secretargas in the Argasinae and placement of Carios and Chiropterargas in the Ornithodorinae (Mans et al., 2019). The Carios clade and its constituent subgenera remain controversial, since the phylogenetic position of its type species Carios (Carios) vespertilionis Latreille, 1796 (formerly Argas vespertilionis) has not been determined with confidence. The current study aimed to resolve Carios sensu lato Klompen and Oliver, 1993, and Carios sensu stricto Hoogstraal, 1985, by determining and analysing phylogenetic nuclear and mitochondrial markers for C. (C.) vespertilionis. Both the nuclear and mitochondrial markers support placement of Carios s.s. within the subfamily Ornithodorinae, but to the exclusion of the clade that includes the 6 other subgenera that are part of Carios s.l. Klompen and Oliver (1993), namely Alectorobius, Antricola, Nothoaspis, Parantricola, Reticulinasus and Subparmatus. These 6 subgenera form a monophyletic clade that might be placed as new subgenera within the genus Alectorobius, or elevated to genera. Given the substantial differences in biology among these subgenera, we propose that these 6 subgenera be elevated to genera. Thus, we propose to modify the classification scheme of Mans et al. (2019) so that the subfamily Argasinae now has six genera, Alveonasus, Argas (subgenera Argas and Persicargas), Navis, Ogadenus, Proknekalia and Secretargas, and the subfamily Ornithodorinae has nine genera, Alectorobius, Antricola (subgenera Antricola and Parantricola), Carios, Chiropterargas, Nothoaspis, Ornithodoros (subgenera Microargas, Ornamentum, Ornithodoros, Pavlovskyella and Theriodoros), Otobius, Reticulinasus and Subparmatus (genera indicated in bold).

Applications of Blocker Nucleic Acids and Non-Metazoan PCR Improves the Discovery of the Eukaryotic Microbiome in Ticks.
Yurie Taya; Gohta Kinoshita; Wessam Mohamed Ahmed Mohamed; Mohamed Abdallah Mohamed Moustafa; Shohei Ogata; Elisha Chatanga; Yuma Ohari; Kodai Kusakisako; Keita Matsuno; Nariaki Nonaka; Ryo Nakao
Microorganisms, 9, 5, 13 May 2021, [International Magazine]
English, Scientific journal, Ticks serve as important vectors of a variety of pathogens. Recently, the viral and prokaryotic microbiomes in ticks have been explored using next-generation sequencing to understand the physiology of ticks and their interactions with pathogens. However, analyses of eukaryotic communities in ticks are limited, owing to the lack of suitable methods. In this study, we developed new methods to selectively amplify microeukaryote genes in tick-derived DNA by blocking the amplification of the 18S rRNA gene of ticks using artificial nucleic acids: peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). In addition, another PCR using non-metazoan primers, referred to as UNonMet-PCR, was performed for comparison. We performed each PCR using tick-derived DNA and sequenced the amplicons using the Illumina MiSeq platform. Almost all sequences obtained by conventional PCR were derived from ticks, whereas the proportion of microeukaryotic reads and alpha diversity increased upon using the newly developed method. Additionally, the PNA- or LNA-based methods were suitable for paneukaryotic analyses, whereas the UNonMet-PCR method was particularly sensitive to fungi. The newly described methods enable analyses of the eukaryotic microbiome in ticks. We expect the application of these methods to improve our understanding of the tick microbiome.

Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis.
Naoki Nomura; Keita Matsuno; Masashi Shingai; Marumi Ohno; Toshiki Sekiya; Ryosuke Omori; Yoshihiro Sakoda; Robert G Webster; Hiroshi Kida
Virology, 557, 55, 61, May 2021, [International Magazine]
English, Scientific journal, Genetic reassortment of influenza A viruses through cross-species transmission contributes to the generation of pandemic influenza viruses. To provide information on the ecology of influenza viruses, we have been conducting a global surveillance of zoonotic influenza and establishing an influenza virus library. Of 4580 influenza virus strains in the library, 3891 have been isolated from over 70 different bird species. The remaining 689 strains were isolated from humans, pigs, horses, seal, whale, and the environment. Phylogenetic analyses of the HA genes of the library isolates demonstrate that the library strains are distributed to all major known clusters of the H1, H2 and H3 subtypes of HA genes that are prevalent in humans. Since past pandemic influenza viruses are most likely genetic reassortants of zoonotic and seasonal influenza viruses, a vast collection of influenza A virus strains from various hosts should be useful for vaccine preparation and diagnosis for future pandemics.

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

Metagenomic identification, sequencing, and genome analysis of porcine hepe-astroviruses (bastroviruses) in porcine feces in Japan.
Makoto Nagai; Tamaki Okabayashi; Masataka Akagami; Aya Matsuu; Yoshikazu Fujimoto; Md Abul Hashem; Hirohisa Mekata; Ryo Nakao; Keita Matsuno; Yukie Katayama; Mami Oba; Tsutomu Omatsu; Tetsuo Asai; Keisuke Nakagawa; Hiroshi Ito; Hiroo Madarame; Kazuhiro Kawai; Toshihiro Ito; Nariaki Nonaka; Kyoko Tsukiyama-Kohara; Yasuo Inoshima; Tetsuya Mizutani; Naoaki Misawa
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 88, 104664, 104664, Mar. 2021, [International Magazine]
English, Scientific journal, Recently, hepe-astrovirus-like RNA viruses named bastroviruses (BastVs), have been found in human, pig, bat, and rat fecal samples. In this study, we determined nearly complete genome sequences of four BastVs in the feces of healthy pigs. Genetic characterization revealed that these porcine BastVs (PBastVs) and BastVs from other animals including humans, had the same genome organization, that is, they contained three predicted conserved domains of viral methyltransferase, RNA helicase, and RdRp in the nonstructural ORF1 and the astrovirus capsid domain in the structural ORF2. Phylogenetic analyses using RNA-dependent RNA polymerase and the capsid region revealed that PBastVs branched with bat and rat BastVs; however, the groups formed by each host were distantly related to human BastVs. Pairwise amino acid sequence comparison demonstrated that PBastVs shared 95.2-98.6% and 76.1-95.5% sequence identity among each other in the ORF1 and ORF2 regions, respectively; the sequence identities between PBastVs and BastVs from other animals were 21.4-42.5% and 9.1-20.6% in the ORF1 and ORF2 regions, respectively. This suggested that BastVs were derived from a common ancestor but evolved independently in each host population during a prolonged period. Putative recombination events were identified in the PBastV genome, suggesting that PBastVs gain sequence diversity and flexibility through recombination events. In an analysis of previously obtained metagenomic data, PBastV sequence reads were detected in 7.3% (23/315) of fecal samples from pigs indicating that PBastVs are distributed among pig populations in Japan.

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

Efficacy of Oral Vaccine against Classical Swine Fever in Wild Boar and Estimation of the Disease Dynamics in the Quantitative Approach.
Enkhbold Bazarragchaa; Norikazu Isoda; Taksoo Kim; Madoka Tetsuo; Satoshi Ito; Keita Matsuno; Yoshihiro Sakoda
Viruses, 13, 2, 20 Feb. 2021, [International Magazine]
English, Scientific journal, Classical swine fever virus (CSFV) in the wild boar population has been spreading in Japan, alongside outbreaks on pigs, since classical swine fever (CSF) reemerged in September 2018. The vaccination using oral bait vaccine was initially implemented in Gifu prefecture in March 2019. In the present study, antibodies against CSFV in wild boar were assessed in 1443 captured and dead wild boars in Gifu prefecture. After the implementation of oral vaccination, the increase of the proportion of seropositive animals and their titer in wild boars were confirmed. Quantitative analysis of antigen and antibodies against CSFV in wild boar implies potential disease diversity in the wild boar population. Animals with status in high virus replication (Ct < 30) and non- or low-immune response were confirmed and were sustained at a certain level after initial oral vaccination. Through continuous vaccination periods, the increase of seroprevalence among wild boar and the decrease of CSFV-positive animals were observed. The epidemiological analysis based on the quantitative virological outcomes could provide more information on the efficacy of oral vaccination and dynamics of CSF in the wild boar population, which will help to improve the implementation of control measures for CSF in countries such as Japan and neighboring countries.

Author Correction: Data mining and model-predicting a global disease reservoir for low-pathogenic Avian Influenza (AI) in the wider Pacific Rim using big data sets.
Marina Gulyaeva; Falk Huettmann; Alexander Shestopalov; Masatoshi Okamatsu; Keita Matsuno; Duc-Huy Chu; Yoshihiro Sakoda; Alexandra Glushchenko; Elaina Milton; Eric Bortz
Scientific reports, 11, 1, 3758, 3758, 08 Feb. 2021, [International Magazine]
English

Spiroplasma Infection among Ixodid Ticks Exhibits Species Dependence and Suggests a Vertical Pattern of Transmission.
Shohei Ogata; Wessam Mohamed Ahmed Mohamed; Kodai Kusakisako; May June Thu; Yongjin Qiu; Mohamed Abdallah Mohamed Moustafa; Keita Matsuno; Ken Katakura; Nariaki Nonaka; Ryo Nakao
Microorganisms, 9, 2, 08 Feb. 2021, [International Magazine]
English, Scientific journal, Members of the genus Spiroplasma are Gram-positive bacteria without cell walls. Some Spiroplasma species can cause disease in arthropods such as bees, whereas others provide their host with resistance to pathogens. Ticks also harbour Spiroplasma, but their role has not been elucidated yet. Here, the infection status and genetic diversity of Spiroplasma in ticks were investigated using samples collected from different geographic regions in Japan. A total of 712 ticks were tested for Spiroplasma infection by PCR targeting 16S rDNA, and Spiroplasma species were genetically characterized based on 16S rDNA, ITS, dnaA, and rpoB gene sequences. A total of 109 samples originating from eight tick species were positive for Spiroplasma infection, with infection rates ranging from 0% to 84% depending on the species. A linear mixed model indicated that tick species was the primary factor associated with Spiroplasma infection. Moreover, certain Spiroplasma alleles that are highly adapted to specific tick species may explain the high infection rates in Ixodes ovatus and Haemaphysalis kitaokai. A comparison of the alleles obtained suggests that horizontal transmission between tick species may not be a frequent event. These findings provide clues to understand the transmission cycle of Spiroplasma species in wild tick populations and their roles in host ticks.

Amblyomma testudinarium infestation on a brown bear (Ursus arctos yesoensis) captured in Hokkaido, a northern island of Japan.
Ryo Nakao; Kohei Shinjo; Tomoki Sakiyama; Shohei Ogata; Kodai Kusakisako; Gohta Kinoshita; Doaa Naguib; Elisha Chatanga; Wessam Mohamed Ahmed Mohamed; Mohamed Abdallah Mohamed Moustafa; Keita Matsuno; Takuya Ito; Nariaki Nonaka; Mariko Sashika; Toshio Tsubota; Michito Shimozuru
Parasitology international, 80, 102209, 102209, Feb. 2021, [International Magazine]
English, Scientific journal, The tick Amblyomma testudinarium Koch, 1844 (Acari: Ixodidae) is known as a vector of several pathogens such as Rickettsia tamurae and severe fever with thrombocytopenia syndrome (SFTS) virus. This tick species is present in many Asian countries, including Japan, where its distribution is limited to the warm areas of Kanto region and the southwestern region. The present study reports the recovery of a partially engorged A. testudinarium from a wild brown bear captured in Shari town, Hokkaido. In addition to morphological identification, the specimen was genetically characterized by the complete mitochondrial genome sequencing. The results showed that the length of the obtained mitogenome is 14,835 bp that encodes 13 protein-coding, two ribosomal RNA (rRNA) (12S and 16S), and 22 transfer RNA genes with two non-coding control regions. The phylogenetic analysis indicated that our sample clustered with A. testudinarium from Nara, Japan, but separated from A. testudinarium from China. Although the introduction of the tick through livestock transportation cannot be ruled out, the detection of A. testudinarium in Hokkaido prefecture, which is separated from the main island where A. testudinarium is present in the south, may suggest the introduction by migratory birds. This study provides important insights on the distribution and host range of A. testudinarium. This will be useful for the future taxonomic analysis of ticks based on the complete mitogenome sequencing. To our knowledge, this is the northernmost detection point of the tropical tick A. testudinarium.

A New Variant Among Newcastle Disease Viruses Isolated in the Democratic Republic of the Congo in 2018 and 2019.
Augustin T Twabela; Lam Thanh Nguyen; Justin Masumu; Patrick Mpoyo; Serge Mpiana; Julienne Sumbu; Masatoshi Okamatsu; Keita Matsuno; Norikazu Isoda; Bianca Zecchin; Isabella Monne; Yoshihiro Sakoda
Viruses, 13, 2, 20 Jan. 2021, [International Magazine]
English, Scientific journal, Newcastle disease (ND) is a highly transmissible and devastating disease that affects poultry and wild birds worldwide. Comprehensive knowledge regarding the characteristics and epidemiological factors of the ND virus (NDV) is critical for the control and prevention of ND. Effective vaccinations can prevent and control the spread of the NDV in poultry populations. For decades, the Democratic Republic of the Congo (DRC) has reported the impacts of ND on commercial and traditional poultry farming systems. The reports were preliminary clinical observations, and few cases were confirmed in the laboratory. However, data on the phylogenetic, genetic, and virological characteristics of NDVs circulating in the DRC are not available. In this study, the whole-genome sequences of three NDV isolates obtained using the next-generation sequencing method revealed two isolates that were a new variant of NDV, and one isolate that was clustered in the subgenotype VII.2. All DRC isolates were velogenic and were antigenically closely related to the vaccine strains. Our findings reveal that despite the circulation of the new variant, ND can be controlled in the DRC using the current vaccine. However, epidemiological studies should be conducted to elucidate the endemicity of the disease so that better control strategies can be implemented.

Phylogenies from mitochondrial genomes of 120 species of ticks: Insights into the evolution of the families of ticks and of the genus Amblyomma.
Samuel Kelava; Ben J Mans; Renfu Shao; Mohamed Abdallah Mohamed Moustafa; Keita Matsuno; Ai Takano; Hiroki Kawabata; Kozue Sato; Hiromi Fujita; Chen Ze; Olivier Plantard; Sandor Hornok; Shan Gao; Dayana Barker; Stephen C Barker; Ryo Nakao
Ticks and tick-borne diseases, 12, 1, 101577, 101577, Jan. 2021, [International Magazine]
English, Scientific journal, The evolution and phylogenetic relationships of the ticks at both the family and genus levels are contested. The genus Amblyomma and its subgenera are in a state of flux; moreover, the relationships among the three tick families are controversial due to conflicting phylogenetic support for different arrangements of the three families of living ticks. With 18 newly sequenced mitochondrial (mt) genomes of ticks included, we executed the largest mt genome phylogenetic study of ticks so far. Phylogenetic trees were inferred from one sea spider mt genome, one horseshoe crab, five mite mt genomes and 146 tick mt genomes from 120 species: 153 mt genomes in total. Sixteen phylogenetic trees were inferred from 10 datasets using both maximum likelihood and Bayesian inference methods. We describe the first novel mt gene-arrangement for the metastriate Ixodidae in Amblyomma (Africaniella) transversale. Also, three unusual partial 16S rRNA gene inserts were found in the mt genome of Haemaphysalis (Alloceraea) kitaokai: we consider the possible role of past genome translocation events in the formation of these inserts. Our phylogenies revealed evidence that: (i) the genus Amblyomma is polyphyletic with respect to Amblyomma (Africaniella) transversale; (ii) the subgenus Aponomma is apparently embedded in the genus Amblyomma; (iii) Haemaphysalis (Segalia) parva and Haemaphysalis (Alloceraea) kitaokai form a clade to the exclusion of other Haemaphysalis species; and (iv) the phylogenetic position of the family Nuttalliellidae is unstable among phylogenies from different datasets.

The NF-κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses.
Crystal A Mendoza; Satoko Yamaoka; Yoshimi Tsuda; Keita Matsuno; Carla M Weisend; Hideki Ebihara
Antiviral research, 185, 104993, 104993, Jan. 2021, [International Magazine]
English, Scientific journal, Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we used them as a platform to screen potential compounds that inhibit viral RNA synthesis. We demonstrated that the NF-κB inhibitor, SC75741, reduces viral RNA synthesis of SFTSV and HRTV using our MG platform and validated these results using infectious SFTSV and HRTV. These results may lead to the use of MG systems as potential screening systems for the identification of antiviral compounds and yield novel insights into host-factors that could play role in bandavirus transcription and replication.

Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness.
Hirotaka Hayashi; Norikazu Isoda; Enkhbold Bazarragchaa; Naoki Nomura; Keita Matsuno; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
Vaccines, 8, 4, 16 Dec. 2020, [International Magazine]
English, Scientific journal, H4 influenza viruses have been isolated from birds across the world. In recent years, an H4 influenza virus infection has been confirmed in pigs. Pigs play an important role in the transmission of influenza viruses to human hosts. Therefore, it is important to develop a new vaccine in the case of an H4 influenza virus infection in humans, considering that this virus has a different antigenicity from seasonal human influenza viruses. In this study, after selecting vaccine candidate strains based on their antigenic relation to one of the pig isolates, A/swine/Missouri/A01727926/2015 (H4N6) (MO/15), an inactivated whole-particle vaccine was prepared from A/swan/Hokkaido/481102/2017 (H4N6). This vaccine showed high immunogenicity in mice, and the antibody induced by the vaccine showed high cross-reactivity to the MO/15 virus. This vaccine induced sufficient neutralizing antibodies and mitigated the effects of an MO/15 infection in a mouse model. This study is the first to suggest that an inactivated whole-particle vaccine prepared from an influenza virus isolated from wild birds is an effective countermeasure in case of a future influenza pandemic caused by the H4 influenza virus.

Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens.
Augustin Twabela; Masatoshi Okamatsu; Keita Matsuno; Norikazu Isoda; Yoshihiro Sakoda
Viruses, 12, 12, 08 Dec. 2020, [International Magazine]
English, Scientific journal, Control measures in the case of high pathogenicity avian influenza (HPAI) outbreaks in poultry include culling, surveillance, and biosecurity; wild birds in captivity may also be culled, although some rare bird species should be rescued for conservation. In this study, two anti-influenza drugs, baloxavir marboxil (BXM) and peramivir (PR), used in humans, were examined in treating HPAI in birds, using chickens as a model. Chickens were infected with H5N6 HPAI virus and were treated immediately or 24 h from challenge with 20 mg/kg BXM or PR twice a day for five days. As per our findings, BXM significantly reduced virus replication in organs and provided full protection to chickens compared with that induced by PR. In the 24-h-delayed treatment, neither drug completely inhibited virus replication nor ensured the survival of infected chickens. A single administration of 2.5 mg/kg of BXM was determined as the minimum dose required to fully protect chickens from HPAI virus; the concentration of baloxavir acid, the active form of BXM, in chicken blood at this dose was sufficient for a 48 h antiviral effect post-administration. Thus, these data can be a starting point for the use of BXM and PR in treating captive wild birds infected with HPAI virus.

Data mining and model-predicting a global disease reservoir for low-pathogenic Avian Influenza (A) in the wider pacific rim using big data sets.
Marina Gulyaeva; Falk Huettmann; Alexander Shestopalov; Masatoshi Okamatsu; Keita Matsuno; Duc-Huy Chu; Yoshihiro Sakoda; Alexandra Glushchenko; Elaina Milton; Eric Bortz
Scientific reports, 10, 1, 16817, 16817, 08 Oct. 2020, [International Magazine]
English, Scientific journal, Avian Influenza (AI) is a complex but still poorly understood disease; specifically when it comes to reservoirs, co-infections, connectedness and wider landscape perspectives. Low pathogenic (Low-path LP) AI in chickens caused by less virulent strains of AI viruses (AIVs)-when compared with highly pathogenic AIVs (HPAIVs)-are not even well-described yet or known how they contribute to wider AI and immune system issues. Co-circulation of LPAIVs with HPAIVs suggests their interactions in their ecological aspects. Here we show for the Pacific Rim an international approach how to data mine and model-predict LP AI and its ecological niche with machine learning and open access data sets and geographic information systems (GIS) on a 5 km pixel size for best-possible inference. This is based on the best-available data on the issue (~ 40,827 records of lab-analyzed field data from Japan, Russia, Vietnam, Mongolia, Alaska and Influenza Research Database (IRD) and U.S. Department of Agriculture (USDA) database sets, as well as 19 GIS data layers). We sampled 157 hosts and 110 low-path AIVs with 32 species as drivers. The prevalence across low-path AIV subtypes is dominated by Muscovy ducks, Mallards, Whistling Swans and gulls also emphasizing industrial impacts for the human-dominated wildlife contact zone. This investigation sets a good precedent for the study of reservoirs, big data mining, predictions and subsequent outbreaks of HPAI and other pandemics.

北海道斜里町においてエゾヒグマより採集されたタカサゴキララマダニの一例
下鶴 倫人; 新庄 康平; 崎山 智樹; 小方 昌平; 草木迫 浩大; 木下 豪太; Mohamed Wessam Mohamed Ahmed; Moustafa Mohamed Abdallah Mohamed; 松野 啓太; 伊東 拓也; 野中 成晃; 佐鹿 万里子; 坪田 敏男; 中尾 亮
日本獣医学会学術集会講演要旨集, 163回, 327, 327, (公社)日本獣医学会, Oct. 2020
Japanese, Symposium

2016-2017年のベトナム南部での疫学的研究から明らかになった、鳥インフルエンザウイルスの新たなホットスポットの意義(The implication of a new hot spot of avian influenza based on epidemiological study in southern Vietnam in 2016-2017)
Le Trung Kien; 磯田 典和; Nguyen Thanh Lam; Chu Duc-Huy; Tien Tien Ngoc; 松野 啓太; 岡松 正敏; 喜田 宏; 迫田 義博; 北海道大人獣共通感染症リサーチセンター/国際協働ユニット
日本獣医学会学術集会講演要旨集, 163回, 232, 232, (公社)日本獣医学会, Oct. 2020
English

コンゴ民主共和国で分離された新たなニューカッスル病ウイルスの性状(Characterization of novel Newcastle disease viruses isolated in the Democratic Republic of Congo)
Twabela Augustin; Mpoyo Patrick; Masumu Justin; Zecchin Bianca; Monne Isabela; 岡松 正敏; 松野 啓太; 迫田 義博; 北海道大人獣共通感染症リサーチセンター/国際協働ユニット
日本獣医学会学術集会講演要旨集, 163回, 233, 233, (公社)日本獣医学会, Oct. 2020
English

ウイルス学的解析および疫学的解析を用いた北海道十勝地方における牛ウイルス性下痢ウイルスの伝播経路解明
廣瀬 静香; 野津 昂亮; 松野 啓太; 岡松 正敏; 川本 恵子; 磯田 典和; 迫田 義博
日本獣医学会学術集会講演要旨集, 163回, 236, 236, (公社)日本獣医学会, Oct. 2020
Japanese

日本の岐阜県にてイノシシから採取した血中古典的ブタ熱ウイルス抗原と抗体に関する定量分析(Quantitative analysis of antigen and antibody of classical swine fever virus in wild boar sera collected in Gifu prefecture, Japan)
Enkhbold Bazarragchaa; 金 琢洙; 哲翁 まどか; 磯田 典和; 松野 啓太; 迫田 義博; 北海道大人獣共通感染症リサーチセンター/国際協働ユニット
日本獣医学会学術集会講演要旨集, 163回, 243, 243, (公社)日本獣医学会, Oct. 2020
English

Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019.
Ankhanbaatar Ulaankhuu; Enkhbold Bazarragchaa; Masatoshi Okamatsu; Takahiro Hiono; Khishgee Bodisaikhan; Tsolmon Amartuvshin; Jargalsaikhan Tserenjav; Tsogtbaatar Urangoo; Khanui Buyantogtokh; Keita Matsuno; Takanari Hattori; Tatsunari Kondoh; Masahiro Sato; Yoshihiro Takadate; Shiho Torii; Mao Isono; Kosuke Okuya; Takeshi Saito; Nodoka Kasajima; Yurie Kida; Junki Maruyama; Manabu Igarashi; Ayato Takada; Hiroshi Kida; Damdinjav Batchuluun; Yoshihiro Sakoda
Virus genes, 56, 4, 472, 479, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country.

Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice.
Hirotaka Hayashi; Masatoshi Okamatsu; Honami Ogasawara; Naoko Tsugawa; Norikazu Isoda; Keita Matsuno; Yoshihiro Sakoda
Nutrients, 12, 7, 05 Jul. 2020, [International Magazine]
English, Scientific journal, Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)2D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D3 [25(OH)D3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D3 and were challenged with the influenza virus. In the lungs of 25(OH)D3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D3 suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.

Efficacy of Neuraminidase Inhibitors against H5N6 Highly Pathogenic Avian Influenza Virus in a Nonhuman Primate Model.
Cong Thanh Nguyen; Saori Suzuki; Yasushi Itoh; Hirohito Ishigaki; Misako Nakayama; Kaori Hayashi; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida; Kazumasa Ogasawara
Antimicrobial agents and chemotherapy, 64, 7, 23 Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Attention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used nonhuman primates to elucidate the pathogenesis of H5N6 HPAIV as well as to determine the efficacy of antiviral drugs against the virus. H5N6 HPAIV infection led to high fever in cynomolgus macaques. The lung injury caused by the virus was severe, with diffuse alveolar damage and neutrophil infiltration. In addition, an increase in interferon alpha (IFN-α) showed an inverse correlation with virus titers during the infection process. Oseltamivir was effective for reducing H5N6 HPAIV propagation, and continuous treatment with peramivir reduced virus propagation and the severity of symptoms in the early stage. This study also showed pathologically severe lung injury states in cynomolgus macaques infected with H5N6 HPAIV, even in those that received early antiviral drug treatments, indicating the need for close monitoring and further studies on virus pathogenicity and new antiviral therapies.

Spatiotemporal and risk analysis of H5 highly pathogenic avian influenza in Vietnam, 2014-2017.
Lam Thanh Nguyen; Mark A Stevenson; Simon M Firestone; Leslie D Sims; Duc Huy Chu; Long Van Nguyen; Tien Ngoc Nguyen; Kien Trung Le; Norikazu Isoda; Keita Matsuno; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
Preventive veterinary medicine, 178, 104678, 104678, May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The aim of this study was to describe the spatiotemporal distribution of H5 HPAI outbreak reports for the period 2014-2017 and to identify factors associated with H5 HPAI outbreak reports. Throughout the study period, a total of 139 outbreaks of H5 HPAI in poultry were reported, due to either H5N1 (96 outbreaks) or H5N6 (43 outbreaks) subtype viruses. H5N1 HPAI outbreaks occurred in all areas of Vietnam while H5N6 HPAI outbreaks were only reported in the northern and central provinces. We counted the number of H5N1 and H5N6 outbreak report-positive districts per province over the four-year study period and calculated the provincial-level standardized morbidity ratio for H5N1 and H5N6 outbreak reports as the observed number of positive districts divided by the expected number. A mixed-effects, zero-inflated Poisson regression model was developed to identify risk factors for outbreak reports of each H5N1 and H5N6 subtype virus. Spatially correlated and uncorrelated random effects terms were included in this model to identify areas of the country where outbreak reports occurred after known risk factors had been accounted-for. The presence of an outbreak report in a province in the previous 6-12 months increased the provincial level H5N1 outbreak report risk by a factor of 2.42 (95% Bayesian credible interval [CrI] 1.27-4.60) while 1000 bird increases in the density of chickens decreased provincial level H5N6 outbreak report risk by a factor of 0.65 (95% CrI 0.38 to 0.97). We document distinctly different patterns in the spatial and temporal distribution of H5N1 and H5N6 outbreak reports. Most of the variation in H5N1 report risk was accounted-for by the fixed effects included in the zero-inflated Poisson model. In contrast, the amount of unaccounted-for risk in the H5N6 model was substantially greater than the H5N1 model. For H5N6 we recommend that targeted investigations should be carried out in provinces with relatively large spatially correlated random effect terms to identify likely determinants of disease. Similarly, investigations should be carried out in provinces with relatively low spatially correlated random effect terms to identify protective factors for disease and/or reasons for failure to report.

E190V substitution of H6 hemagglutinin is one of key factors for binding to sulfated sialylated glycan receptor and infection to chickens.
Yuto Kikutani; Masatoshi Okamatsu; Shoko Nishihara; Sayaka Takase-Yoden; Takahiro Hiono; Robert P de Vries; Ryan McBride; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
Microbiology and immunology, 64, 4, 304, 312, Apr. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Avian influenza viruses (AIVs) recognize sialic acid linked α2,3 to galactose (SAα2,3Gal) glycans as receptors. In this study, the interactions between hemagglutinins (HAs) of AIVs and sulfated SAα2,3Gal glycans were analyzed to clarify the molecular basis of interspecies transmission of AIVs from ducks to chickens. It was revealed that E190V and N192D substitutions of the HA increased the recovery of viruses derived from an H6 duck virus isolate, A/duck/Hong Kong/960/1980 (H6N2), in chickens. Recombinant HAs from an H6 chicken virus, A/chicken/Tainan/V156/1999 (H6N1), bound to sulfated SAα2,3Gal glycans, whereas the HAs from an H6 duck virus did not. Binding preference of mutant HAs revealed that an E190V substitution is critical for the recognition of sulfated SAα2,3Gal glycans. These results suggest that the binding of the HA from H6 AIVs to sulfated SAα2,3Gal glycans explains a part of mechanisms of interspecies transmission of AIVs from ducks to chickens.

Development of a High-Throughput Serum Neutralization Test Using Recombinant Pestiviruses Possessing a Small Reporter Tag.
Madoka Tetsuo; Keita Matsuno; Tomokazu Tamura; Takasuke Fukuhara; Taksoo Kim; Masatoshi Okamatsu; Norbert Tautz; Yoshiharu Matsuura; Yoshihiro Sakoda
Pathogens (Basel, Switzerland), 9, 3, 04 Mar. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, A serum neutralization test (SNT) is an essential method for the serological diagnosis of pestivirus infections, including classical swine fever, because of the cross reactivity of antibodies against pestiviruses and the non-quantitative properties of antibodies in an enzyme-linked immunosorbent assay. In conventional SNTs, an immunoperoxidase assay or observation of cytopathic effect after incubation for 3 to 7 days is needed to determine the SNT titer, which requires labor-intensive or time-consuming procedures. Therefore, a new SNT, based on the luciferase system and using classical swine fever virus, bovine viral diarrhea virus, and border disease virus possessing the 11-amino-acid subunit derived from NanoLuc luciferase was developed and evaluated; this approach enabled the rapid and easy determination of the SNT titer using a luminometer. In the new method, SNT titers can be determined tentatively at 2 days post-infection (dpi) and are comparable to those obtained by conventional SNTs at 3 or 4 dpi. In conclusion, the luciferase-based SNT can replace conventional SNTs as a high-throughput antibody test for pestivirus infections.

Genetic and antigenic characterization of the first H7N7 low pathogenic avian influenza viruses isolated in Vietnam.
Kien Trung Le; Masatoshi Okamatsu; Lam Thanh Nguyen; Keita Matsuno; Duc-Huy Chu; Tien Ngoc Tien; Tung Thanh Le; Hiroshi Kida; Yoshihiro Sakoda
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 78, 104117, 104117, Mar. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, During the annual surveillance of avian influenza viruses (AIVs) in Vietnam in 2018, three H7N7 AIV isolates were identified in domestic ducks in a single flock in Vinh Long province. The present study is the first documented report of H7N7 virus isolates in Vietnam and aimed to characterize these viruses, both genetically and antigenically. Deduced amino acid sequences for the hemagglutinins (HAs) indicated a low pathogenicity of these viruses in chickens. Phylogenetic analysis revealed that the H7 HA genes of these isolates were closely related to each other and belonged to the European-Asian sublineage, together with those of H7N3 viruses isolated from ducks in Cambodia during 2017. They were not genetically related to those of Chinese H7N9 or H7N1 viruses that were previously detected in Vietnam during 2012. Interestingly, the M genes of the two H7N7 virus isolates were phylogenetically classified into distinct groups, suggesting an ongoing reassortment event in domestic ducks because they were isolated from the same flock. These H7N7 viruses exhibited somewhat different antigenic characteristics compared with other representative H7 low pathogenic AIVs. Surprisingly, the antigenicity of Vietnamese H7N7 viruses is similar to Chinese H7N9 highly pathogenic AIV. The findings of this study suggest that H7N7 viruses may be undergoing reassortment and antigenic diversification in poultry flocks in Vietnam. The silent spread of Vietnamese H7N7 viruses in chickens may lead to acquire high pathogenicity in chickens although the zoonotic potential of the viruses seems to be low since these viruses retain typical avian-specific motifs in the receptor-binding site in the HA and there is no mutation related to mammalian adaptation in PB2 gene. Thus, these results highlight the need for continuous and intensive surveillance of avian influenza in Vietnam, targeting not only highly pathogenic AIVs but also low pathogenic viruses.

A cloned classical swine fever virus derived from the vaccine strain GPE- causes cytopathic effect in CPK-NS cells via type-I interferon-dependent necroptosis.
Yukari Itakura; Keita Matsuno; Asako Ito; Markus Gerber; Matthias Liniger; Yuri Fujimoto; Tomokazu Tamura; Ken-Ichiro Kameyama; Masatoshi Okamatsu; Nicolas Ruggli; Hiroshi Kida; Yoshihiro Sakoda
Virus research, 276, 197809, 197809, 15 Jan. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Classical swine fever viruses (CSFVs) do typically not show cytopathic effect (CPE) in cell culture, while some strains such as vaccine strain the GPE- induce CPE in the swine kidney-derived CPK-NS cell line cultured in serum-free medium. These latter strains commonly lack Npro-mediated inhibition of type-I interferon (IFN) induction. In order to explore the molecular mechanisms of GPE--induced CPE, we analyzed the cellular pathways involved. In CPK-NS cells infected with the attenuated-vaccine-derived vGPE- strain, both, apoptosis and necroptosis were induced. Necroptosis was type-I IFN-dependent and critical for visible CPE. In contrast, the parental virulent vALD-A76 strain did not induce any of these pathways nor CPE. We used reverse genetics to investigate which viral factors regulate these cell-death pathways. Interestingly, a mutant vGPE- in which the Npro function was restored to inhibit type-I IFN induction did not induce necroptosis nor CPE but still induced apoptosis, while an Npro-mutant vALD-A76 incapable of inhibiting type-I IFN production induced necroptosis and CPE. Although Erns of CSFV is reportedly involved in controlling apoptosis, apoptosis induction by vGPE- or apoptosis inhibition by vALD-A76 were independent of the unique amino acid difference found in Erns of these two strains. Altogether, these results demonstrate that type-I IFN-dependent necroptosis related to non-functional Npro is the main mechanism for CPE induction by vGPE-, and that viral factor(s) other than Erns may induce or inhibit apoptosis in vGPE- or vALD-A76 infected CPK-NS cells, respectively.

Molecular, antigenic, and pathogenic characterization of H5N8 highly pathogenic avian influenza viruses isolated in the Democratic Republic of Congo in 2017.
Augustin T Twabela; Masatoshi Okamatsu; Georges Mbuyi Tshilenge; Serge Mpiana; Justin Masumu; Lam Thanh Nguyen; Keita Matsuno; Isabella Monne; Bianca Zecchin; Yoshihiro Sakoda
Archives of virology, 165, 1, 87, 96, Jan. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, In May 2017, high mortality of chickens and Muscovy ducks due to the H5N8 highly pathogenic avian influenza virus (HPAIV) was reported in the Democratic Republic of Congo (DR Congo). In this study, we assessed the molecular, antigenic, and pathogenic features in poultry of the H5N8 HPAIV from the 2017 Congolese outbreaks. Phylogenetic analysis of the eight viral gene segments revealed that all 12 DR Congo isolates clustered in clade 2.3.4.4B together with other H5N8 HPAIVs isolated in Africa and Eurasia, suggesting a possible common origin of these viruses. Antigenically, a slight difference was observed between the Congolese isolates and a representative virus from group C in the same clade. After intranasal inoculation with a representative DR Congo virus, high pathogenicity was observed in chickens and Muscovy ducks but not in Pekin ducks. Viral replication was higher in chickens than in Muscovy duck and Pekin duck organs; however, neurotropism was pronounced in Muscovy ducks. Our data confirmed the high pathogenicity of the DR Congo virus in chickens and Muscovy ducks, as observed in the field. National awareness and strengthening surveillance in the region are needed to better control HPAIVs.

Nearly Complete Genome Sequence of a Newcastle Disease Virus Strain Isolated from a Wild Garganey (Spatula querquedula) in Russia.
Alexandra V Glushchenko; Tatyana Y Alikina; Kseniya S Yurchenko; Egor V Shekunov; Marina A Gulyaeva; Keita Matsuno; Masatoshi Okamatsu; Marsel R Kabilov; Alexander M Shestopalov
Microbiology resource announcements, 8, 50, 12 Dec. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, This work describes the nearly complete genome sequence of Newcastle disease virus (NDV) strain NDV/Novosibirsk/garganey/27/2014, which was isolated from a wild garganey in western Siberia, Russia. The NDV strain was classified as belonging to class II of genotype I and was identified as having recent common ancestry with isolates from wild and domestic birds in China and South Korea.

Broad and systemic immune-modulating capacity of plant-derived dsRNA.
Takara Hajake; Keita Matsuno; Dacquin M Kasumba; Haruka Oda; Moe Kobayashi; Nao Miyata; Madoka Shinji; Amane Kogure; Nodoka Kasajima; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroki Kato; Takashi Fujita
International immunology, 31, 12, 811, 821, 08 Nov. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Double-stranded RNA (dsRNA) is well characterized as an inducer of anti-viral interferon responses. We previously reported that dsRNA extracted from a specific edible plant possesses an immune-modulating capacity to confer, in mice, resistance against respiratory viruses, including the H1N1 strain of the influenza A virus (IAV). We report here that the systemic immune-activating capacity of the plant-derived dsRNA protected mice from infection by a highly virulent H5N1 strain of the IAV. In addition, subcutaneous inoculation of the dsRNA together with the inactivated virion of the H5N1 strain of the IAV suppressed the lethality of the viral infection as compared with individual inoculation of either dsRNA or HA protein, suggesting its potential usage as a vaccination adjuvant. Moreover, intra-peritoneal inoculation of the dsRNA limited the growth of B16-F10 melanoma cells through the activation of NK cells in murine models. Taken together, this study demonstrated the systemic immune-modulating capacity of a plant-derived dsRNA and its potential for nucleic acid-based clinical applications.

The first isolation and identification of canine parvovirus (CPV) type 2c variants during 2016-2018 genetic surveillance of dogs in Mongolia.
Uyangaa Temuujin; Ariunaa Tserendorj; Jumpei Fujiki; Yoshihiro Sakoda; Erdene-Ochir Tseren-Ochir; Masatoshi Okamatsu; Keita Matsuno; Tumenjargal Sharav; Motohiro Horiuchi; Takashi Umemura; Tungalag Chultemdorj
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 73, 269, 275, Sep. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Canine parvovirus type 2 (CPV-2) causes a highly contagious and fatal disease, developing into acute hemorrhagic enteritis and myocarditis, in dogs. CPV-2 has evolved, generating antigenic variants CPV-2a/2b/2c that are globally distributed. However, investigating molecular characterization of CPV-2 among dog populations in Mongolia has been limited. Herein, 42 stool samples were collected from dogs with clinical signs of infection, and conventional PCR assays were employed to detect CPV-2 in 23. Our results indicated that during 2016-2018, the new CPV-2a and 2c subtypes were detected in 34.7% of the samples, and the new CPV-2b subtype was detected in 30.4% of samples. VP2 protein sequence analysis and next-generation sequencing of the complete viral genome confirmed these antigenic types. However, sequence analysis indicated new and unreported mutations, Pro580Thr, and Tyr584His in the CPV-2c subtype. From a PCR-positive sample, CPV-2c was successfully isolated, and we performed an immunofluorescence assay for antigen detection. Additionally, we performed genetic characterization and phylogenetic analysis to investigate genetic diversity among isolates from the region, resulting in high CPV-2 genetic diversity in the Mongolian dog population. Striking similarities were also observed between sequences of the strains isolated from Mongolia and China over a similar time span.

重症熱性血小板減少症候群ウイルスの核タンパク質Nと結合する宿主RNAの機能解明
水間 奎太; 松野 啓太; 岡松 正敏; 高田 礼人; 迫田 義博
日本獣医学会学術集会講演要旨集, 162回, 390, 390, (公社)日本獣医学会, Aug. 2019
Japanese

ベトナムで初単離されたH7N7低病原性鳥インフルエンザウイルスの遺伝学的性状および抗原性の解析(Genetic and antigenic characterization of H7N7 low pathogenic avian influenza viruses firstly isolated in Vietnam)
Le Trung Kien; Nguyen Thanh Lam; Chu Duc-Huy; Nguyen Tien Ngoc; Nguyen Long Van; Tien Tien Ngoc; 松野 啓太; 岡松 正敏; 喜田 宏; 迫田 義博
日本獣医学会学術集会講演要旨集, 162回, 392, 392, (公社)日本獣医学会, Aug. 2019
English

鶏の高病原性鳥インフルエンザウイルス感染に対する抗ウイルス薬の作用(Effect of antiviral drugs against highly pathogenic avian influenza virus infection in chickens)
Augustin T. Twabela; 岡松 正敏; 松野 啓太; 迫田 義博
日本獣医学会学術集会講演要旨集, 162回, 392, 392, (公社)日本獣医学会, Aug. 2019
English

発光タグHiBiTをレポーターとして用いた遺伝子組換えウイルスによる簡便なペスチウイルス抗体測定法の確立
哲翁 まどか; 松野 啓太; 田村 友和; 福原 崇介; 松浦 善治; 岡松 正敏; 迫田 義博
日本獣医学会学術集会講演要旨集, 162回, 393, 393, (公社)日本獣医学会, Aug. 2019
Japanese

海外から持ち込まれた携帯品非加熱家きん畜産物から分離されたH7N3亜型高病原性鳥インフルエンザウイルスの性状解析
柴田 明弘; 原田 理恵子; 岡松 正敏; 松野 啓太; 有田 知子; 鈴木 康司; 白倉 雅之; 小田切 孝人; 竹前 喜洋; 内田 裕子; 西藤 岳彦; 迫田 義博; 尾坂 優之
日本獣医学会学術集会講演要旨集, 162回, 395, 395, (公社)日本獣医学会, Aug. 2019
Japanese

マダニ中のフレボウイルスの遺伝子系統解析に基づく性状推定
松野 啓太; 中尾 亮; 梶原 将大; 下田 宙; 海老原 秀喜; 高田 礼人; 前田 健; 岡松 正敏; 迫田 義博
日本獣医学会学術集会講演要旨集, 162回, 400, 400, (公社)日本獣医学会, Aug. 2019
Japanese

Taxonomy of the order Bunyavirales: update 2019.
Abulikemu Abudurexiti; Scott Adkins; Daniela Alioto; Sergey V Alkhovsky; Tatjana Avšič-Županc; Matthew J Ballinger; Dennis A Bente; Martin Beer; Éric Bergeron; Carol D Blair; Thomas Briese; Michael J Buchmeier; Felicity J Burt; Charles H Calisher; Chénchén Cháng; Rémi N Charrel; Il Ryong Choi; J Christopher S Clegg; Juan Carlos de la Torre; Xavier de Lamballerie; Fēi Dèng; Francesco Di Serio; Michele Digiaro; Michael A Drebot; Xiǎoméi Duàn; Hideki Ebihara; Toufic Elbeaino; Koray Ergünay; Charles F Fulhorst; Aura R Garrison; George Fú Gāo; Jean-Paul J Gonzalez; Martin H Groschup; Stephan Günther; Anne-Lise Haenni; Roy A Hall; Jussi Hepojoki; Roger Hewson; Zhìhóng Hú; Holly R Hughes; Miranda Gilda Jonson; Sandra Junglen; Boris Klempa; Jonas Klingström; Chūn Kòu; Lies Laenen; Amy J Lambert; Stanley A Langevin; Dan Liu; Igor S Lukashevich; Tāo Luò; Chuánwèi Lǚ; Piet Maes; William Marciel de Souza; Marco Marklewitz; Giovanni P Martelli; Keita Matsuno; Nicole Mielke-Ehret; Maria Minutolo; Ali Mirazimi; Abulimiti Moming; Hans-Peter Mühlbach; Rayapati Naidu; Beatriz Navarro; Márcio Roberto Teixeira Nunes; Gustavo Palacios; Anna Papa; Alex Pauvolid-Corrêa; Janusz T Pawęska; Jié Qiáo; Sheli R Radoshitzky; Renato O Resende; Víctor Romanowski; Amadou Alpha Sall; Maria S Salvato; Takahide Sasaya; Shū Shěn; Xiǎohóng Shí; Yukio Shirako; Peter Simmonds; Manuela Sironi; Jin-Won Song; Jessica R Spengler; Mark D Stenglein; Zhèngyuán Sū; Sùróng Sūn; Shuāng Táng; Massimo Turina; Bó Wáng; Chéng Wáng; Huálín Wáng; Jūn Wáng; Tàiyún Wèi; Anna E Whitfield; F Murilo Zerbini; Jìngyuàn Zhāng; Lěi Zhāng; Yànfāng Zhāng; Yong-Zhen Zhang; Yújiāng Zhāng; Xueping Zhou; Lìyǐng Zhū; Jens H Kuhn
Archives of virology, 164, 7, 1949, 1965, Jul. 2019, [Peer-reviewed], [International Magazine]
English, In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

A systematic study towards evolutionary and epidemiological dynamics of currently predominant H5 highly pathogenic avian influenza viruses in Vietnam.
Lam Thanh Nguyen; Simon M Firestone; Mark A Stevenson; Neil D Young; Leslie D Sims; Duc Huy Chu; Tien Ngoc Nguyen; Long Van Nguyen; Tung Thanh Le; Hung Van Nguyen; Hung Nam Nguyen; Tien Ngoc Tien; Tho Dang Nguyen; Bich Ngoc Tran; Keita Matsuno; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
Scientific reports, 9, 1, 7723, 7723, 22 May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, This study aimed to elucidate virus, host and environmental dynamics of Vietnamese H5 highly pathogenic avian influenza viruses (HPAIVs) during 2014-2017. Epidemiologically, H5 HPAIVs were frequently detected in apparently healthy domestic and Muscovy ducks and therefore these are preferred species for H5 HPAIV detection in active surveillance. Virologically, clade 2.3.2.1c and 2.3.4.4 H5 HPAIVs were predominant and exhibited distinct phylogeographic evolution. Clade 2.3.2.1c viruses clustered phylogenetically in North, Central and South regions, whilst clade 2.3.4.4 viruses only detected in North and Central regions formed small groups. These viruses underwent diverse reassortment with existence of at least 12 genotypes and retained typical avian-specific motifs. These H5 HPAIVs exhibited large antigenic distance from progenitor viruses and commercial vaccines currently used in poultry. Bayesian phylodynamic analysis inferred that clade 2.3.2.1c viruses detected during 2014-2017 were likely descended from homologous clade viruses imported to Vietnam previously and/or preexisting Chinese viruses during 2012-2013. Vietnamese clade 2.3.4.4 viruses closely shared genetic traits with contemporary foreign spillovers, suggesting that there existed multiple transboundary virus dispersals to Vietnam. This study provides insights into the evolution of Vietnamese H5 HPAIVs and highlights the necessity of strengthening control measures such as, preventive surveillance and poultry vaccination.

Rapid and sensitive detection of elephant endotheliotropic herpesvirus 1 (EEHV1) in blood by loop-mediated isothermal amplification (LAMP).
Kazuya Takehana; Teruo Kinjyo; Manabu Nemoto; Keita Matsuno
The Journal of veterinary medical science, 81, 3, 504, 507, 30 Mar. 2019, [Peer-reviewed], [Domestic magazines]
English, Elephant endotheliotropic herpesvirus type 1 (EEHV1) is the most important causative agent of an acute fatal hemorrhagic disease in Asian elephants (Elephas maximus). We employed loop-mediated isothermal amplification (LAMP) to develop a rapid and simple detection method for EEHV1 in blood. When used to test 21 clinical samples collected in Japan, the EEHV1 assay correctly identified one positive and 20 negative clinical samples. It was observed that when samples were spiked with synthetic DNA plasmids including EEHV1 polymerase gene, the detection limit of the LAMP assay was 101.2 copies/µl and 100-fold higher than that of conventional PCR. These advantages of the LAMP assay for EEHV1 detection may facilitate better veterinary practices for treating elephants suffering from the acute disease.

Characterization of a novel reassortant H7N3 highly pathogenic avian influenza virus isolated from a poultry meat product taken on a passenger flight to Japan.
Akihiro Shibata; Rieko Harada; Masatoshi Okamatsu; Keita Matsuno; Tomoko Arita; Yasushi Suzuki; Masayuki Shirakura; Takato Odagiri; Nobuhiro Takemae; Yuko Uchida; Takehiko Saito; Yoshihiro Sakoda; Hiroyuki Osaka
The Journal of veterinary medical science, 81, 3, 444, 448, 20 Mar. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A new reassortant H7N3 avian influenza virus (AIV) was isolated from a duck meat product that was illegally taken on board a passenger flight from China to Japan in March 2018. Sequencing analysis revealed that the H7N3 isolate, A/duck/Japan/AQ-HE30-1/2018 (Dk/HE30-1) (H7N3), was a reassortant highly pathogenic avian influenza virus (HPAIV) that contained the haemagglutinin (HA) gene of Chinese H7N9 HPAIV. Dk/HE30-1 (H7N3) possessed a novel polybasic sequence motif PEVPKRRRTAR/GLF at the HA cleavage site that has never previously been reported in H7 HPAIVs. The HA antigenicity of Dk/HE30-1 (H7N3) slightly differed from that of H7N9 HPAIVs previously reported. These findings will help further our knowledge of the circulation and genetic evolution of emerging AIVs in endemic areas.

Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil.
Keiichi Taniguchi; Yoshinori Ando; Haruaki Nobori; Shinsuke Toba; Takeshi Noshi; Masanori Kobayashi; Makoto Kawai; Ryu Yoshida; Akihiko Sato; Takao Shishido; Akira Naito; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroshi Kida
Scientific reports, 9, 1, 3466, 3466, 05 Mar. 2019, [Peer-reviewed], [International Magazine]
English, Human infections with avian-origin influenza A(H7N9) virus represent a serious threat to global health; however, treatment options are limited. Here, we show the inhibitory effects of baloxavir acid (BXA) and its prodrug baloxavir marboxil (BXM), a first-in-class cap-dependent endonuclease inhibitor, against A(H7N9), in vitro and in vivo. In cell culture, BXA at four nanomolar concentration achieved a 1.5-2.8 log reduction in virus titers of A(H7N9), including the NA-R292K mutant virus and highly pathogenic avian influenza viruses, whereas NA inhibitors or favipiravir required approximately 20-fold or higher concentrations to achieve the same levels of reduction. A(H7N9)-specific amino acid polymorphism at position 37, implicated in BXA binding to the PA endonuclease domain, did not impact on BXA susceptibility. In mice, oral administration of BXM at 5 and 50 mg/kg twice a day for 5 days completely protected from a lethal A/Anhui/1/2013 (H7N9) challenge, and reduced virus titers more than 2-3 log in the lungs. Furthermore, the potent therapeutic effects of BXM in mice were still observed when a higher virus dose was administered or treatment was delayed up to 48 hours post infection. These findings support further investigation of BXM for A(H7N9) treatment in humans.

Evaluation of a rapid isothermal nucleic acid amplification kit, Alere™ i Influenza A&B, for the detection of avian influenza viruses.
Enkhbold Bazarragchaa; Masatoshi Okamatsu; Ankhanbaatar Ulaankhuu; Augustin Tshibwabwa Twabela; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
Journal of virological methods, 265, 121, 125, Mar. 2019, [Peer-reviewed], [International Magazine]
English, Rapid and accurate diagnosis of influenza virus infection is essential for quick responses for both human and animal health. The Alere™ i Influenza A&B is a novel isothermal nucleic acid amplification kit that can detect and differentiate between influenza A and B viruses in human specimens in approximately 15 min. In the present study, the performance of the Alere™ i Influenza A&B kit was evaluated for its ability to detect avian influenza virus in chickens. The kit was able to detect representative avian influenza virus strains (hemagglutinin subtypes H1-H16, including the recently isolated H5 and H7 highly pathogenic avian influenza viruses), and the detection limit of the kit for these viruses varied between 10-1.4-102.1 50% egg-infective dose per test, which is higher than the analytical sensitivity of the antigen detection immunochromatography kit ESPLINE® A INFLUENZA. In experimentally infected chickens inoculated with a highly pathogenic avian influenza virus strain A/chicken/Hokkaido/002/2016 (H5N6), viral RNA was detected in the tracheal and cloacal swabs. These results indicate that this kit has the potential to be used as a rapid screening test of influenza A virus infection in chickens.

Diversity of spotted fever group rickettsiae and their association with host ticks in Japan.
May June Thu; Yongjin Qiu; Keita Matsuno; Masahiro Kajihara; Akina Mori-Kajihara; Ryosuke Omori; Naota Monma; Kazuki Chiba; Junji Seto; Mutsuyo Gokuden; Masako Andoh; Hideo Oosako; Ken Katakura; Ayato Takada; Chihiro Sugimoto; Norikazu Isoda; Ryo Nakao
Scientific reports, 9, 1, 1500, 1500, 06 Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Spotted fever group (SFG) rickettsiae are obligate intracellular Gram-negative bacteria mainly associated with ticks. In Japan, several hundred cases of Japanese spotted fever, caused by Rickettsia japonica, are reported annually. Other Rickettsia species are also known to exist in ixodid ticks; however, their phylogenetic position and pathogenic potential are poorly understood. We conducted a nationwide cross-sectional survey on questing ticks to understand the overall diversity of SFG rickettsiae in Japan. Out of 2,189 individuals (19 tick species in 4 genera), 373 (17.0%) samples were positive for Rickettsia spp. as ascertained by real-time PCR amplification of the citrate synthase gene (gltA). Conventional PCR and sequencing analyses of gltA indicated the presence of 15 different genotypes of SFG rickettsiae. Based on the analysis of five additional genes, we characterised five Rickettsia species; R. asiatica, R. helvetica, R. monacensis (formerly reported as Rickettsia sp. In56 in Japan), R. tamurae, and Candidatus R. tarasevichiae and several unclassified SFG rickettsiae. We also found a strong association between rickettsial genotypes and their host tick species, while there was little association between rickettsial genotypes and their geographical origins. These observations suggested that most of the SFG rickettsiae have a limited host range and are maintained in certain tick species in the natural environment.

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

A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity
Haruhiko Fujihira; Katsuaki Usami; Keita Matsuno; Hideyuki Takeuchi; Kaori Denda-Nagai; Jun-Ichi Furukawa; Yasuro Shinohara; Ayato Takada; Yoshihiro Kawaoka; Tatsuro Irimura
Scientific Reports, 8, 1, 5495, Nature Publishing Group, 01 Dec. 2018, [Peer-reviewed]
English, Scientific journal

Repeated detection of H7N9 avian influenza viruses in raw poultry meat illegally brought to Japan by international flight passengers.
Akihiro Shibata; Masatoshi Okamatsu; Riho Sumiyoshi; Keita Matsuno; Zu-Jyun Wang; Hiroshi Kida; Hiroyuki Osaka; Yoshihiro Sakoda
Virology, 524, 10, 17, Nov. 2018, [Peer-reviewed], [International Magazine]
English, H7N9 highly and low pathogenic avian influenza viruses (HPAIV and LPAIV, respectively) have been isolated from duck meat products that were brought illegally into Japan by flight passengers in their hand luggage. These H7N9 virus isolates were phylogenetically closely related to those prevailing in China. Antigenic analysis revealed that the hemagglutinin of the H7N9 HPAIV isolate was slightly different from those of the H7N9 LPAIV and older H7 strains. These meat products contaminated with AIVs repeatedly brought into Japan lead to increased risks of poultry and public health. Continuous border disease control based on the detection and culling of infected poultry and meat products is, thus, essential for the prevention of introduction and spread of AIVs.

Fatal Tickborne Phlebovirus Infection in Captive Cheetahs, Japan.
Keita Matsuno; Noriyuki Nonoue; Ayako Noda; Nodoka Kasajima; Keita Noguchi; Ai Takano; Hiroshi Shimoda; Yasuko Orba; Mieko Muramatsu; Yoshihiro Sakoda; Ayato Takada; Shinji Minami; Yumi Une; Shigeru Morikawa; Ken Maeda
Emerging infectious diseases, 24, 9, 1726, 1729, Sep. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Two captive cheetahs from a zoo in Japan died of a severe fever with thrombocytopenia syndrome-like illness. Severe fever with thrombocytopenia syndrome virus, an endemic tickborne phlebovirus, was detected systemically with secretion of infectious viruses into the saliva. These cases highlight the risk for exposure of captive animals to endemic arthropodborne pathogens.

H13 influenza viruses in wild birds have undergone genetic and antigenic diversification in nature.
Zu-Jyun Wang; Yuto Kikutani; Lam Thanh Nguyen; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Scott Krauss; Richard Webby; Youn-Jeong Lee; Hiroshi Kida; Yoshihiro Sakoda
Virus genes, 54, 4, 543, 549, Aug. 2018, [Peer-reviewed], [International Magazine]
English, Among 16 haemagglutinin (HA) subtypes of avian influenza viruses (AIVs), H13 AIVs have rarely been isolated in wild waterfowl. H13 AIVs cause asymptomatic infection and are maintained mainly in gull and tern populations; however, the recorded antigenic information relating to the viruses has been limited. In this study, 2 H13 AIVs, A/duck/Hokkaido/W345/2012 (H13N2) and A/duck/Hokkaido/WZ68/2012 (H13N2), isolated from the same area in the same year in our surveillance, were genetically and antigenically analyzed with 10 representative H13 strains including a prototype strain, A/gull/Maryland/704/1977 (H13N6). The HA genes of H13 AIVs were phylogenetically divided into 3 groups (I, II, and III). A/duck/Hokkaido/W345/2012 (H13N2) was genetically classified into Group III. This virus was distinct from a prototype strain, A/gull/Maryland/704/1977 (H13N6), and the virus, A/duck/Hokkaido/WZ68/2012 (H13N2), both belonging to Group I. Antigenic analysis indicated that the viruses of Group I were antigenically closely related to those of Group II, but distinct from those of Group III, including A/duck/Hokkaido/W345/2012 (H13N2). In summary, our study indicates that H13 AIVs have undergone antigenic diversification in nature.

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

Isolation and characterization of avian influenza viruses from raw poultry products illegally imported to Japan by international flight passengers
A. Shibata; T. Hiono; H. Fukuhara; R. Sumiyoshi; A. Ohkawara; K. Matsuno; M. Okamatsu; H. Osaka; Y. Sakoda
Transboundary and Emerging Diseases, 65, 2, 465, 475, Blackwell Publishing Ltd, 01 Apr. 2018, [Peer-reviewed]
English, Scientific journal

Potency of an inactivated influenza vaccine prepared from A/duck/Mongolia/245/2015 (H10N3) against H10 influenza virus infection in a mouse model
Mizuho Suzuki; Masatoshi Okamatsu; Yuri Fujimoto; Takahiro Hiono; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
Japanese Journal of Veterinary Research, 66, 1, 29, 41, Hokkaido University, 2018, [Peer-reviewed]
English, Scientific journal

A cross-sectional study to quantify the prevalence of avian influenza viruses in poultry at intervention and non-intervention live bird markets in central Vietnam, 2014
D. -H. Chu; M. A. Stevenson; L. V. Nguyen; N. Isoda; S. M. Firestone; T. N. Nguyen; L. T. Nguyen; K. Matsuno; M. Okamatsu; H. Kida; Y. Sakoda
TRANSBOUNDARY AND EMERGING DISEASES, 64, 6, 1991, 1999, Dec. 2017, [Peer-reviewed]
English, Scientific journal

Potency of an inactivated influenza vaccine prepared from A/duck/Hokkaido/162/2013 (H2N1) against a challenge with A/swine/Missouri/2124514/2006 (H2N3) in mice
Mizuho Suzuki; Masatoshi Okamatsu; Takahiro Hiono; Keita Matsuno; Yoshihiro Sakoda
JOURNAL OF VETERINARY MEDICAL SCIENCE, 79, 11, 1815, 1821, Nov. 2017, [Peer-reviewed]
English, Scientific journal

Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor
Tatsunari Kondoh; Rashid Manzoor; Naganori Nao; Junki Maruyama; Wakako Furuyama; Hiroko Miyamoto; Asako Shigeno; Makoto Kuroda; Keita Matsuno; Daisuke Fujikura; Masahiro Kajihara; Reiko Yoshida; Manabu Igarashi; Ayato Takada
PLOS ONE, 12, 10, e0186450, Oct. 2017, [Peer-reviewed]
English, Scientific journal

Selection of antigenic variants of an H5N1 highly pathogenic avian influenza virus in vaccinated chickens
Lam Thanh Nguyen; Tatsuya Nishi; Shintaro Shichinohe; Duc-Huy Chu; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Hiroshi Kida; Yoshihiro Sakoda
VIROLOGY, 510, 252, 261, Oct. 2017, [Peer-reviewed]
English, Scientific journal

Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild and captive birds in the winter season of 2016-2017 in Northern Japan
Takahiro Hiono; Masatoshi Okamatsu; Keita Matsuno; Atsushi Haga; Ritsuko Iwata; Lam Thanh Nguyen; Mizuho Suzuki; Yuto Kikutani; Hiroshi Kida; Manabu Onuma; Yoshihiro Sakoda
MICROBIOLOGY AND IMMUNOLOGY, 61, 9, 387, 397, Sep. 2017, [Peer-reviewed]
English, Scientific journal

Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against highly pathogenic avian influenza virus belonging to the genetic clade 2.3.4.4
Lam Thanh Nguyen; Kazunari Nakaishi; Keiko Motojima; Ayako Ohkawara; Erina Minato; Junki Maruyama; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Takashi Kimura; Ayato Takada; Hiroshi Kida; Yoshihiro Sakoda
PLOS ONE, 12, 8, e0182228, Aug. 2017, [Peer-reviewed]
English, Scientific journal

Genetic and virulence characterization of classical swine fever viruses isolated in Mongolia from 2007 to 2015
Bazarragchaa Enkhbold; Munkhduuren Shatar; Shiho Wakamori; Tomokazu Tamura; Takahiro Hiono; Keita Matsuno; Masatoshi Okamatsu; Takashi Umemura; Batchuluun Damdinjav; Yoshihiro Sakoda
VIRUS GENES, 53, 3, 418, 425, Jun. 2017, [Peer-reviewed]
English, Scientific journal

Antigenic diversity of H5 highly pathogenic avian influenza viruses of clade 2.3.4.4 isolated in Asia
Ayako Ohkawara; Masatoshi Okamatsu; Makoto Ozawa; Duc-Huy Chu; Lam Thanh Nguyen; Takahiro Hiono; Keita Matsuno; Hiroshi Kida; Yoshihiro Sakoda
MICROBIOLOGY AND IMMUNOLOGY, 61, 5, 149, 158, May 2017, [Peer-reviewed]
English, Scientific journal

Potency of whole virus particle and split virion vaccines using dissolving microneedle against challenges of H1N1 and H5N1 influenza viruses in mice
Akihiro Nakatsukasa; Koji Kuruma; Masatoshi Okamatsu; Takahiro Hiono; Mizuho Suzuki; Keita Matsuno; Hiroshi Kida; Takayoshi Oyamada; Yoshihiro Sakoda
VACCINE, 35, 21, 2855, 2861, May 2017, [Peer-reviewed]
English, Scientific journal

Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016
Masatoshi Okamatsu; Makoto Ozawa; Kosuke Soda; Hiroki Takakuwa; Atsushi Haga; Takahiro Hiono; Aya Matsuu; Yuko Uchida; Ritsuko Iwata; Keita Matsuno; Masakazu Kuwahara; Toshiyo Yabuta; Tatsufumi Usui; Hiroshi Ito; Manabu Onuma; Yoshihiro Sakoda; Takehiko Saito; Koichi Otsuki; Toshihiro Ito; Hiroshi Kida
EMERGING INFECTIOUS DISEASES, 23, 4, 691, 695, Apr. 2017, [Peer-reviewed]
English, Scientific journal

Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection
Keita Matsuno; Yasuko Orba; Kimberly Maede-White; Dana Scott; Friederike Feldmann; Mifang Liang; Hideki Ebihara
FRONTIERS IN MICROBIOLOGY, 8, 104, Jan. 2017, [Peer-reviewed]
English, Scientific journal

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

Genetic and antigenic characterization of H5, H6 and H9 avian influenza viruses circulating in live bird markets with intervention in the center part of Vietnam
Duc-Huy Chu; Masatoshi Okamatsu; Keita Matsuno; Takahiro Hiono; Kohei Ogasawara; Lam Thanh Nguyen; Long Van Nguyen; Tien Ngoc Nguyen; Thuy Thu Nguyen; Dong Van Pham; Dang Hoang Nguyen; Tho Dang Nguyen; Thanh Long To; Hung Van Nguyen; Hiroshi Kida; Yoshihiro Sakoda
VETERINARY MICROBIOLOGY, 192, 194, 203, Aug. 2016, [Peer-reviewed]
English, Scientific journal

Is the optimal pH for membrane fusion in host cells by avian influenza viruses related to host range and pathogenicity?
Masatoshi Okamatsu; Yurie Motohashi; Takahiro Hiono; Tomokazu Tamura; Kazuki Nagaya; Keita Matsuno; Yoshihiro Sakoda; Hiroshi Kida
ARCHIVES OF VIROLOGY, 161, 8, 2235, 2242, Aug. 2016, [Peer-reviewed]
English, Scientific journal

AN EPIZOOTIC OF EMERGING NOVEL AVIAN POX IN CARRION CROWS (CORVUS CORONE) AND LARGE-BILLED CROWS (CORVUS MACRORHYNCHOS) IN JAPAN
Daisuke Fukui; Makiko Nakamura; Tsuyoshi Yamaguchi; Makiko Takenaka; Mami Murakami; Tokuma Yanai; Hideto Fukushi; Kazumi Yanagida; Gen Bando; Keita Matsuno; Masashi Nagano; Toshio Tsubota
JOURNAL OF WILDLIFE DISEASES, 52, 2, 230, 241, Apr. 2016, [Peer-reviewed]
English, Scientific journal

Complete genome sequence of the avian paramyxovirus serotype 5 strain APMV-5/budgerigar/Japan/TI/75
Takahiro Hiono; Keita Matsuno; Kotaro Tuchiya; Zhifeng Lin; Masatoshi Okamatsu; Yoshihiro Sakoda
Genome Announcements, 4, 5, American Society for Microbiology, 2016, [Peer-reviewed]
English, Scientific journal

Experimental infection of highly and low pathogenic avian influenza viruses to chicken's, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission
Takahiro Hiono; Masatoshi Okamatsu; Naoki Yamamoto; Kohei Ogasawara; Mayumi Endo; Saya Kuribayashi; Shintaro Shichinohe; Yurie Motohashi; Duc-Huy Chu; Mizuho Suzuki; Takaya Ichikawa; Tatsuya Nishi; Yuri Abe; Keita Matsuno; Kazuyuki Tanaka; Tsutomu Tanigawa; Hiroshi Kida; Yoshihiro Sakoda
VETERINARY MICROBIOLOGY, 182, 108, 115, Jan. 2016, [Peer-reviewed]
English, Scientific journal

Intracellular membrane association of classical swine fever virus NS4B is critical for viral RNA replication
Tomokazu Tamura; Nicolas Ruggli; Masatoshi Okamatsu; Keita Matsuno; Yoshihiro Sakoda
Nov. 2015, [Peer-reviewed]
Japanese, Research society

豚コレラウイルスの病原性発現の分子基盤
田村友和; Nicolas Ruggli; 岡松正敏; 松野啓太; 迫田義博
Nov. 2015, [Peer-reviewed]
Japanese, Research society

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

豚コレラウイルス非構造蛋白NS4Bの機能と病原性に及ぼす影響
田村友和; Nicolas Ruggli; 長島尚史; 岡松正敏; Artur Summerfield; 松野啓太; 喜田宏; 迫田義博
Jul. 2015, [Peer-reviewed]
Japanese, Research society

Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus
Makoto Kuroda; Daisuke Fujikura; Asuka Nanbo; Andrea Marzi; Osamu Noyori; Masahiro Kajihara; Junki Maruyama; Keita Matsuno; Hiroko Miyamoto; Reiko Yoshida; Heinz Feldmann; Ayato Takada
JOURNAL OF VIROLOGY, 89, 12, 6481, 6493, Jun. 2015, [Peer-reviewed]
English, Scientific journal

Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to the Retrospective Identification of Taxonomically Unassigned Bunyaviruses and the Discovery of a Novel Member of the Genus Phlebovirus
Keita Matsuno; Carla Weisend; Masahiro Kajihara; Colette Matysiak; Brandi N. Williamson; Martin Simuunza; Aaron S. Mweene; Ayato Takada; Robert B. Tesh; Hideki Ebihara
JOURNAL OF VIROLOGY, 89, 1, 594, 604, Jan. 2015, [Peer-reviewed]
English, Scientific journal

Differential potential for envelope glycoprotein-mediated steric shielding of host cell surface proteins among filoviruses
Osamu Noyori; Keita Matsuno; Masahiro Kajihara; Eri Nakayama; Manabu Igarashi; Makoto Kuroda; Norikazu Isoda; Reiko Yoshida; Ayato Takada
VIROLOGY, 446, 1-2, 152, 161, Nov. 2013, [Peer-reviewed]
English, Scientific journal

Characterization of the Bhanja serogroup viruses (Bunyaviridae): a novel species of the genus Phlebovirus and its relationship with other emerging tick-borne phleboviruses.
Matsuno K; Weisend C; Travassos da Rosa AP; Anzick SL; Dahlstrom E; Porcella SF; Dorward DW; Yu XJ; Tesh RB; Ebihara H
Journal of virology, 87, 7, 3719, 3728, Apr. 2013, [Peer-reviewed]

エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明
藤平 陽彦; 宇佐美 克明; 伝田 香里; 松野 啓太; 篠原 康郎; 佐藤 あやの; 高田 礼人; 入村 達郎
日本生化学会大会プログラム・講演要旨集, 85回, 3T15, 08, (公社)日本生化学会, Dec. 2012
Japanese

Inhibition of Marburg Virus Budding by Nonneutralizing Antibodies to the Envelope Glycoprotein
Masahiro Kajihara; Andrea Marzi; Eri Nakayama; Takeshi Noda; Makoto Kuroda; Rashid Manzoor; Keita Matsuno; Heinz Feldmann; Reiko Yoshida; Yoshihiro Kawaoka; Ayato Takada
JOURNAL OF VIROLOGY, 86, 24, 13467, 13474, Dec. 2012, [Peer-reviewed]
English, Scientific journal

Complete Genome Sequencing of Four Geographically Diverse Strains of Batai Virus
Allison Groseth; Keita Matsuno; Eric Dahlstrom; Sarah L. Anzick; Stephen F. Porcella; Hideki Ebihara
JOURNAL OF VIROLOGY, 86, 24, 13844, 13845, Dec. 2012, [Peer-reviewed]
English, Scientific journal

Antibody-Dependent Enhancement of Marburg Virus Infection
Eri Nakayama; Daisuke Tomabechi; Keita Matsuno; Noriko Kishida; Reiko Yoshida; Heinz Feldmann; Ayato Takada
JOURNAL OF INFECTIOUS DISEASES, 204, S978, S985, Nov. 2011, [Peer-reviewed]
English, Scientific journal

An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration
Masahiro Kajihara; Keita Matsuno; Edgar Simulundu; Mieko Muramatsu; Osamu Noyori; Rashid Manzoor; Eri Nakayama; Manabu Igarashi; Daisuke Tomabechi; Reiko Yoshida; Masatoshi Okamatsu; Yoshihiro Sakoda; Kimihito Ito; Hiroshi Kida; Ayato Takada
JAPANESE JOURNAL OF VETERINARY RESEARCH, 59, 2-3, 89, 100, Aug. 2011, [Peer-reviewed]
English, Scientific journal

Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin
Katsuaki Usami; Keita Matsuno; Manabu Igarashi; Kaori Denda-Nagai; Ayato Takada; Tatsuro Irimura
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 407, 1, 74, 78, Apr. 2011, [Peer-reviewed]
English, Scientific journal

C-type lectins do not act as functional receptors for filovirus entry into cells
Keita Matsuno; Eri Nakayama; Osamu Noyori; Andrea Marzi; Hideki Ebihara; Tatsuro Irimura; Heinz Feldmann; Ayato Takada
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 403, 1, 144, 148, Dec. 2010, [Peer-reviewed]
English, Scientific journal

Enzyme-Linked Immunosorbent Assay for Detection of Filovirus Species-Specific Antibodies
Eri Nakayama; Ayaka Yokoyama; Hiroko Miyamoto; Manabu Igarashi; Noriko Kishida; Keita Matsuno; Andrea Marzi; Heinz Feldmann; Kimihito Ito; Masayuki Saijo; Ayato Takada
CLINICAL AND VACCINE IMMUNOLOGY, 17, 11, 1723, 1728, Nov. 2010, [Peer-reviewed]
English, Scientific journal

Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory
Yoshihiro Sakoda; Sengee Sugar; Damdinjav Batchluun; Tseren-Ochir Erdene-Ochir; Masatoshi Okamatsu; Norikazu Isoda; Kosuke Soda; Hiroki Takakuwa; Yoshimi Tsuda; Naoki Yamamoto; Noriko Kishida; Keita Matsuno; Eri Nakayama; Masahiro Kajihara; Ayaka Yokoyama; Ayato Takada; Ruuragchaa Sodnomdarjaa; Hiroshi Kida
VIROLOGY, 406, 1, 88, 94, Oct. 2010, [Peer-reviewed]
English, Scientific journal

Different Potential of C-Type Lectin-Mediated Entry between Marburg Virus Strains
Keita Matsuno; Noriko Kishida; Katsuaki Usami; Manabu Igarashi; Reiko Yoshida; Eri Nakayama; Masayuki Shimojima; Heinz Feldmann; Tatsuro Irimura; Yoshihiro Kawaoka; Ayato Takada
JOURNAL OF VIROLOGY, 84, 10, 5140, 5147, May 2010, [Peer-reviewed]
English, Scientific journal

MGL/CD301を介するエボラウイルス感染増強に関わる表層糖蛋白質の構造的特徴(Structural features of Ebola viral envelope glycoproteins responsible for the enhancement of infection through the interaction with MGL/CD301)
宇佐美 克明; 松野 啓太; 五十嵐 学; 伝田 香里; 高田 礼人; 入村 達郎
日本生化学会大会プログラム・講演要旨集, 82回, 4T20p, 16, (公社)日本生化学会, Sep. 2009
English

Classical Swine Fever Virus Can Remain Virulent after Specific Elimination of the Interferon Regulatory Factor 3-Degrading Function of N-pro
Nicolas Ruggli; Artur Summerfield; Ana R. Fiebach; Laurence Guzylack-Piriou; Oliver Bauhofer; Catherine G. Lamm; Sandro Waltersperger; Keita Matsuno; Luzia Liu; Markus Gerber; Kyung H. Choi; Martin A. Hofmann; Yoshihiro Sakoda; Jon-Duri Tratschin
JOURNAL OF VIROLOGY, 83, 2, 817, 829, Jan. 2009, [Peer-reviewed]
English, Scientific journal

Cleavage of the NS2-3 protein in the cells of cattle persistently infected with non-cytopathogenic bovine viral diarrhea virus
Ken-ichiro Kameyama; Yoshihiro Sakoda; Keita Matsuno; Asako Ito; Motoshi Tajima; Shigeyuki Nakamura; Hiroshi Kida
MICROBIOLOGY AND IMMUNOLOGY, 52, 5, 277, 282, May 2008, [Peer-reviewed]
English, Scientific journal

Genetic and pathobiological characterization of bovine viral diarrhea viruses recently isolated from cattle in Japan
Keita Matsuno; Yoshihiro Sakoda; Ken-ichiro Kameyama; Kyuzo Tamai; Asako Ito; Hiroshi Kida
JOURNAL OF VETERINARY MEDICAL SCIENCE, 69, 5, 515, 520, May 2007, [Peer-reviewed]
English, Scientific journal

2024~2025年における野鳥および海生哺乳類のHPAIV感染の確認とモニタリング体制で見えてきた課題
渡辺有希子; 安達光; 服部薫; 松野啓太; 日尾野隆大; 日尾野隆大; 直亨則; 磯田典和; 磯田典和; 迫田義博; 迫田義博; 大沼学; 齊藤慶輔, 北海道獣医師会雑誌, 69, 8, 2025

ダニ媒介性ウイルスの感染リスクに影響する生態学的要因:北海道におけるアライグマとエゾウイルスについて
伊藤萌林; 南川未来; 伊藤萌林; 南川未来; コウバ アナスタシア; 沼田栄花; 伊藤哲治; 野中成晃; 中尾亮; 大森亮介; 尾針由真; 下鶴倫人; 坪田敏男; 松野啓太; 佐鹿万里子, 日本獣医学会学術集会講演要旨集, 167th, 2024

人獣共通感染症対策に資する活動
澤洋文; 澤洋文; 澤洋文; 田畑耕史郎; 板倉友香里; 梶原将大; 林田京子; 松野啓太; 直亨則; 大場靖子; 大場靖子; 佐々木道仁, 日本化学療法学会雑誌, 72, 5, 2024

新規オルソナイロウイルス(エゾウイルス)感染症の病理学的解析および治療薬探索を目的とした致死感染マウスモデルの確立
有泉拓馬; 松野啓太; 松野啓太; 田畑耕史郎; 板倉友香里; 小林広子; 佐々木道仁; 澤洋文; 大場靖子; 澤洋文; 大場靖子, 日本獣医学会学術集会講演要旨集, 167th, 2024

Virological characterization of SFTSV mutant adapted to specific cell lines and its application to develop antiviral compounds
日下部伸治; 宍戸貴雄; 松野啓太; 松野啓太; 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; 佐藤彰彦; 佐藤彰彦, 日本ウイルス学会学術集会プログラム・予稿集(Web), 71st, 2024

Yezo virus infection: A novel tick-borne disease
山口宏樹; 渡慧; 三津橋和也; 田宮和真; 水間奎太; 松野啓太; 松野啓太, 臨床とウイルス, 52, 1, 2024

日本のマダニから検出されたBeiji nairovirusおよび近縁ウイルスの解析
岸本麻衣; 岸本麻衣; 岸本麻衣; 板倉友香里; 板倉友香里; 田畑耕史郎; 田畑耕史郎; 駒込理佳; 山口宏樹; 中尾亮; 邱永晋; 澤洋文; 大場靖子; 松野啓太; 澤洋文; 大場靖子; 松野啓太, 日本獣医学会学術集会講演要旨集, 167th, 2024

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

エゾウイルス発見の経緯
松野啓太; 松野啓太; 児玉文宏; 山口宏樹; 有泉拓馬; 前田健; 西條政幸; 川端寛樹, 日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集(CD-ROM), 97th-71st, 2023

Toward understanding the ticks community dynamics: What determines the number of ticks on raccoons?
伊藤萌林; 南川未来; KOVBA Anastasiia; 田谷友里恵; GITA Pandey Sadaula; THANAKORN Rompo; 馬場佐織; 片田雪; 丹羽志萌; 松野啓太; 中尾亮; 大森亮介; 伊藤哲治; 下鶴倫人; 坪田敏夫; 佐鹿万里子, 日本生態学会大会講演要旨(Web), 70th, 2023

Comparative analysis of the eukaryotic microbiome of ticks among tick species and regions in Japan.
田谷友里恵; MOUSTAFA Mohamed Ahmed Mohamed; 尾針由真; 松野啓太; 野中成晃; 中尾亮, 衛生動物, 74, 2, 2023

Comprehensive microbial analysis of ticks in Japan
田谷友里恵; MOUSTAFA Mohamed; 尾針由真; 松野啓太; 野中成晃; 中尾亮, 日本寄生虫学会大会プログラム・抄録集, 92nd, 2023

Characterization of an orbivirus detected from a tick collected in Shimane prefecture, Japan
藤澤直輝; 中尾亮; 松野啓太, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

Risk assessment of tick-borne virus transmission from ticks using raccoon as a sentinel
伊藤萌林; 松野啓太; 南川未来; 南川未来; 重野麻子; 有泉拓馬; 伊藤哲治; KOVBA Anastasiia; 沼田栄花; 大森亮介; 尾針由真; 中尾亮; 下鶴輪人; 坪田敏男; 佐鹿万里子, 日本野生動物医学会大会・講演要旨集, 29th, 2023

Pathogenicity of Yezo virus, Ama virus, and Iwanai Valley virus in mice
西野綾乃; 西野綾乃; 朴ウンシル; 立本完吾; 井上雄介; 井上雄介; 石嶋慧多; 黒田雄大; MENDOZA Milagros Virhuez; 原田倫子; 原田倫子; 山本つかさ; 山本つかさ; 松村凌; 松村凌; 小林大介; 伊澤晴彦; 葛西真治; 松野啓太; 前田健; 前田健, 日本ウイルス学会学術集会プログラム・予稿集(Web), 70th, 2023

新型コロナウイルス変異株の進化と細胞融合活性の変化
池田輝政; BEGUM MST Monira; NASSER Hesham; 佐藤佳; 松野啓太; 福原崇介, 日本遺伝学会大会プログラム・予稿集, 95th (CD-ROM), 2023

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

北海道で発熱患者から分離された新規オルソナイロウイルス(エゾウイルス)のマウス感染モデルの作製および病態解析
有泉拓馬; 大場靖子; 田畑耕史朗; 板倉友香里; 小林広子; 佐々木道仁; 松野啓太; 澤洋文, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th, 2022

Pathological analyses of Yezo virus infection in a mouse model
有泉拓馬; 大場靖子; 田畑耕史郎; 板倉友香里; 小林広子; 佐々木道仁; 松野啓太; 澤洋文, 日本分子生物学会年会プログラム・要旨集(Web), 45th, 2022

新規ナイロウイルスであるエゾウイルスによる感染症の発見
松野啓太; 松野啓太; 児玉文宏; 児玉文宏; 山口宏樹; 有泉拓馬; 前田健, 日本獣医師会獣医学術学会年次大会講演要旨集, 2022, 2022

Morphological and genetic characteristics of Ixodid Ticks Collected from Cerorhinca monocerata on Teuri Island, Hokkaido, Japan
田谷友里恵; 佐藤遼太郎; 尾針由真; 松野啓太; 綿貫豊; 野中成晃; 中尾亮, 日本寄生虫学会大会プログラム・抄録集, 91st, 2022

マダニ由来培養細胞に持続感染している新規オルビウイルス
松野啓太; 田谷友里恵; 田谷友里恵; 高木善弘; 市居修; 平井美穂; 中尾亮; 布浦拓郎; 松尾栄子, 日本ウイルス学会学術集会プログラム・予稿集(Web), 69th, 2022

ダニ媒介性オルビウイルスの複製機構に関する研究
松尾栄子; 松野啓太; 中尾亮; 佐伯圭一; 林昌宏; 河野潤一, 日本獣医学会学術集会講演要旨集, 165th (CD-ROM), 2022

北海道天売島において渡り性海鳥から発見された未記載マダニ種の形態および遺伝的特徴
田谷友里恵; 佐藤遼太朗; 尾針由真; 松野啓太; 綿貫豊; 野中成晃; 中尾亮, 日本獣医学会学術集会講演要旨集, 165th (CD-ROM), 2022

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

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

ミトゲノムおよびゲノムワイド一塩基多型を用いたフタトゲチマダニの分子遺伝学的解析
尾針由真; 草木迫浩大; 白藤(梅宮)梨可; MOHAMED Wessam Mohamed Ahmed; MOHAMED MOUSTAFA Mohamed Abdallah啓太; CHATANGA Elisha; 松野啓太; BARKER Stephen; 野中成晃; 中尾亮, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

マダニが保有する真核生物叢解析法の開発
田谷友里恵; 木下豪太; MOHAMED Wessam MA; MOUSTAFA Mohamed AM; MOUSTAFA Mohamed AM; 尾針由真; 松野啓太; 野中成晃; 中尾亮, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

インフルエンザウイルスライブラリーを活用したパンデミックインフルエンザ対策
野村直樹; 新開大史; 松野啓太; 関屋俊輝; 関屋俊輝; 大野円実; 磯田典和; 迫田義博; 喜田宏; 喜田宏, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021

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

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

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

北海道における新規オルソナイロウイルス(エゾウイルス:Yezo virus)によるマダニ媒介性急性発熱性疾患の発見
児玉文宏; 枝川峻二; 永坂敦; 松野啓太; 好井健太朗; 澤洋文; 山岸彩沙; 古澤弥; 山口亮; 矢野公一; 山口宏樹; 後藤明子; 駒込理佳; 三好正浩; 伊東拓也; 小山内佑太; 角千春; 堀田明豊; 前田健; 安藤秀二; 西條政幸, IASR (Web), 41, 1, 2020

マウスモデルにおけるインフルエンザウイルス感染に対するビタミンD代謝産物25(OH)D3の経口補給による効果
林裕貴; 岡松正敏; 小笠原帆南; 津川尚子; 磯田典和; 松野啓太; 松野啓太; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 163rd, 2020

鳥インフルエンザウイルスの中間宿主としてのウズラおよびシチメンチョウにおけるシアル酸糖鎖分布の解析
小林大樹; 佐々木乙; 日尾野隆大; 岡松正敏; 西原祥子; 高瀬明; 市居修; 松野啓太; 松野啓太; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 163rd, 2020

Arthropod-borne viruses (arboviruses)
大場靖子; 澤洋文; 松野啓太; 松野啓太, ウイルス, 70, 1, 2020

SFTS発症動物について(ネコ,イヌを中心に)
前田健; 前田健; 野口慧多; 立本完吾; 坂井祐介; 下田宙; 高野愛; 森川茂; 松鵜彩; 桐野有美; 岡林環樹; 早坂大輔; 水谷哲也; 松野啓太; 沖見朝代; 大島寛彰, IASR (Web), 40, 7, 2019

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

動物におけるSFTSV感染の疫学調査
前田健; 前田健; 野口慧多; 立本完吾; 坂井祐介; 下田宙; 高野愛; 森川茂; 松鵜彩; 桐野有美; 岡林環樹; 早坂大輔; 水谷哲也; 松野啓太; 白永伸行; 鈴木和男, IASR (Web), 40, 7, 2019

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

豚コレラの発生を防ぐために―モンゴルでの取り組み―
迫田義博; SHATAR Munkhduuren; ENKHBOLD Bazarragchaa; 廣瀬和彦; 今泉好能; 松野啓太; 岡松正敏; TEMUUJIN Uyangaa; GANZORIG Basan; 梅村孝司, 家畜衛生学雑誌, 44, 2, 92‐93, 14 Dec. 2018
Japanese

チーターにおける重症熱性血小板減少症候群ウイルス感染による死亡例
野々上範之; 野田亜矢子; 中西正人; 松野啓太; 宇根有美; 前田健; 森川茂; 南心司, 動物園水族館雑誌, 60, 2, 57, 25 Sep. 2018
Japanese

海外から持ち込まれた未加熱家きん肉等から分離された高病原性及び低病原性H7N9亜型鳥インフルエンザウイルスの性状解析
柴田明弘; 岡松正敏; 住吉理穂; 松野啓太; 松野啓太; WANG Zu‐Jyun; WANG Zu‐Jyun; 喜田宏; 喜田宏; 尾坂優之; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 161st, 355, 21 Aug. 2018
Japanese

豚コレラウイルス弱毒生ワクチン株GPE-を感染させたCPK‐NS細胞における細胞変性効果のメカニズム
板倉友香里; 松野啓太; 岡松正敏; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 161st, 345, 21 Aug. 2018
Japanese

鳥インフルエンザウイルスのα2,3硫酸化シアル酸糖鎖認識機構の解析
菊谷祐斗; 岡松正敏; 西原祥子; 高瀬明; 松野啓太; 松野啓太; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 161st, 355, 21 Aug. 2018
Japanese

コンゴ民主共和国で2017年に単離されたH5N8高病原性鳥インフルエンザウイルスの性状解析(Characterization of H5N8 Highly Pathogenic Avian Influenza Viruses Isolated in DR Congo in 2017)
Twabela Augustin; Tshilenge George; Nguyen Thanh-Lam; 松野 啓太; Monne Isabella; Zecchin Bianca; 岡松 正敏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 161回, 356, 356, Aug. 2018
(公社)日本獣医学会, English

2014-2017のベトナムにおけるH5高病原性鳥インフルエンザ発生の時空間・リスク解析(Spatiotemporal and risk analysis of H5 highly pathogenic avian influenza occurrence in Vietnam during 2014-2017)
Nguyen Thanh-Lam; Stevenson Mark; Firestone Simon; Sims Les; Chu Huy; Nguyen Long; Nguyen Tien; 磯田 典和; 松野 啓太; 岡松 正敏; 喜田 宏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 161回, 357, 357, Aug. 2018
(公社)日本獣医学会, English

鳥インフルエンザウイルス検出におけるAlere i influenza A&Bの評価(Evaluation of Alere i influenza A&B for the detection of avian influenza virus)
Enkhbold Bazarragchaa; 岡松 正敏; Ulaankhuu Ankhanbaatar; 松野 啓太; 喜田 宏; 新井 宏育; 迫田 義博, 日本獣医学会学術集会講演要旨集, 161回, 357, 357, Aug. 2018
(公社)日本獣医学会, English

SFTS疑いネコに対する確定診断用RT‐PCRの開発
朴ウンシル; 前田健; 松鵜彩; 桐野有美; 藤田修; 宇根有美; 松野啓太; 下島昌幸; 西條政幸; 森川茂, 日本獣医学会学術集会講演要旨集, 161回, 367, 367, Aug. 2018
(公社)日本獣医学会, Japanese

動物園におけるダニ媒介性ウイルス感染症によるチーターの死亡例
松野啓太; 笠島和; 野々上範之; 野田亜矢子; 南心司; 宇根有美; 前田健, 衛生動物, 69, 2, 103, 103, 25 Jun. 2018
日本衛生動物学会, Japanese

動物園におけるダニ媒介性ウイルス感染症によるチーターの死亡例
松野 啓太; 笠島 和; 野々上 範之; 野田 亜矢子; 南 心司; 宇根 有美; 前田 健, 衛生動物, 69, 2, 103, 103, Jun. 2018
日本衛生動物学会, Japanese

人と動物の共通感染症最前線 15 チーターにおける重症熱性血小板減少症候群
樋口真; 宇根有美; 野々上範之; 野田亜矢子; 松野啓太; 南心司; 前田健; 森川茂, 獣医畜産新報, 71, 1161, 258‐260, 260, 01 Apr. 2018
文永堂出版(株), Japanese

【人と動物の共通感染症最前線15】 チーターにおける重症熱性血小板減少症候群
樋口 真; 宇根 有美; 野々上 範之; 野田 亜矢子; 松野 啓太; 南 心司; 前田 健; 森川 茂, 獣医畜産新報, 71, 4, 258, 260, Apr. 2018
文永堂出版(株), Japanese

国内におけるマダニ媒介性フレボウイルスの網羅的調査
下田宙; 水野純子; 南昌平; 青木栞; 鍬田龍星; 高野愛; 松野啓太; 海老原秀樹; 前田健, 衛生動物, 69, Supplement, 61, 61, 30 Mar. 2018
日本衛生動物学会, Japanese

国内におけるマダニ媒介性フレボウイルスの網羅的調査
下田 宙; 水野 純子; 南 昌平; 青木 栞; 鍬田 龍星; 高野 愛; 松野 啓太; 海老原 秀樹; 前田 健, 衛生動物, 69, Suppl., 61, 61, Mar. 2018
日本衛生動物学会, Japanese

Immune-modulating capacity of a plant-derived dsRNA and its potential applications
Takara Hajake; Dacquin Muhandwa Kasumba; Haruka Oda; Keita Matsuno; Masatoshi Okamatsu; Yoshihiro Sakoda; Hiroki Kato; Takashi Fujita, CYTOKINE, 100, 27, 27, Dec. 2017
English, Summary international conference

2016‐2017年冬季に北日本で野鳥及び飼育鳥から分離されたH5N6高病原性鳥インフルエンザウイルスの性状解析
岡松正敏; 日尾野隆大; 菊谷祐斗; 鈴木瑞穂; NGUYEN Thanh‐Lam; 松野啓太; 松野啓太; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 160th, 382, 382, 30 Aug. 2017
(公社)日本獣医学会, Japanese

ミトゲノム解析によるマダニ系統分類法の開発
中尾亮; 木下豪太; 齋藤歩; 邱永晋; 松野啓太; 杉本千尋; 片倉賢, 日本獣医学会学術集会講演要旨集, 160th, 346, 30 Aug. 2017
Japanese

2016‐2017年冬季に北日本で野鳥及び飼育鳥から分離されたH5N6高病原性鳥インフルエンザウイルスの性状解析
岡松正敏; 日尾野隆大; 菊谷祐斗; 鈴木瑞穂; NGUYEN Thanh‐Lam; 松野啓太; 松野啓太; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 160th, 382, 382, 30 Aug. 2017
(公社)日本獣医学会, Japanese

Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against a 2.3.4.4 highly pathogenic avian influenza virus(和訳中)
Nguyen Thanh-Lam; 中石 和成; 本島 桂子; 大河原 彩子; 日尾野 隆大; 松野 啓太; 岡松 正敏; 高田 礼人; 喜田 宏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 160回, 384, 384, Aug. 2017
(公社)日本獣医学会, English

Genetic and antigenic characterization of H13 avian influenza viruses(和訳中)
Wang Zu Jyun; 菊谷 祐斗; Nguyen Thanh-Lam; 松野 啓太; 岡松 正敏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 160回, 385, 385, Aug. 2017
(公社)日本獣医学会, English

2.3.4.4高病原性鳥インフルエンザウイルスに対する新規モノクローナル抗体を用いた免疫クロマトグラフィーキットによるH5ヘマグルチニンの迅速かつ広範囲検出(Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against a 2.3.4.4 highly pathogenic avian influenza virus)
Nguyen Thanh-Lam; 中石 和成; 本島 桂子; 大河原 彩子; 日尾野 隆大; 松野 啓太; 岡松 正敏; 高田 礼人; 喜田 宏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 160回, 384, 384, Aug. 2017
(公社)日本獣医学会, English

H13鳥インフルエンザウイルスの遺伝子と抗原の性状(Genetic and antigenic characterization of H13 avian influenza viruses)
Wang Zu Jyun; 菊谷 祐斗; Nguyen Thanh-Lam; 松野 啓太; 岡松 正敏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 160回, 385, 385, Aug. 2017
(公社)日本獣医学会, English

マダニとそれに共生するCoxiella属細菌の共進化機構の考察 両者の遺伝的多様性と系統学的位置関係より
齋藤 歩; 中尾 亮; Thu May June; 邱 永晋; 松野 啓太; 杉本 千尋; 片倉 賢, 日本獣医学会学術集会講演要旨集, 159回, 340, 340, Aug. 2016
(公社)日本獣医学会, Japanese

ワクチン接種後の鶏におけるH5鳥インフルエンザウイルスの抗原多様性の選択(Selection of antigenic variants of H5 avian influenza viruses in vaccinated chickens)
Nguyen Thanh-Lam; 西 達也; 七戸 新太郎; Chu Duc-Huy; 日尾野 隆大; 松野 啓太; 岡松 正敏; 喜田 宏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 159回, 371, 371, Aug. 2016
(公社)日本獣医学会, English

海外から持ち込まれた未加熱家きん肉から分離された鳥インフルエンザウイルスの性状解析
柴田 明弘; 日尾野 隆大; 福原 久江; 住吉 理穂; 大河原 彩子; 松野 啓太; 岡松 正敏; 迫田 義博; 尾坂 優之, 日本獣医学会学術集会講演要旨集, 159回, 382, 382, Aug. 2016
(公社)日本獣医学会, Japanese

モンゴルにおける豚コレラの発生と分離ウイルスの遺伝子と病原性の解析
迫田 義博; Bazarragchaa Enkhbold; Munkhduuren Shatar; 若森 史穂; 日尾野 隆大; 松野 啓太; 岡松 正敏; Batchuluun Damdinjav; 梅村 孝司, 日本獣医学会学術集会講演要旨集, 159回, 388, 388, Aug. 2016
(公社)日本獣医学会, Japanese

北海道で分離された新規ダニ媒介性フレボウイルスの性状解析
鳥居志保; 鳥居志保; 松野啓太; 松野啓太; 中尾亮; 邱永晋; 梶原将大; 直亨則; 村松美笑子; 海老原秀喜; 高田礼人; 高田礼人, 日本分子生物学会年会プログラム・要旨集(Web), 39th, ROMBUNNO.1LBA‐083 (WEB ONLY), 2016
Japanese

豚コレラウイルス非構造蛋白NS4BのN末端領域の機能解析
田村友和; RUGGLI Nicolas; 松野啓太; 松野啓太; 岡松正敏; 迫田義博; 迫田義博, 日本獣医学会学術集会講演要旨集, 158th, 346, 346, 30 Aug. 2015
(公社)日本獣医学会, Japanese

RT‐PCR法による新規ダニ媒介性フレボウイルス遺伝子の探索
松野啓太; 松野啓太; 下田宙; 鳥居志保; 邱永晋; 中尾亮; 梶原将大; 岡松正敏; 迫田義博; 迫田義博; 奥村敦; 奥村敦; 高田礼人; 高田礼人; 前田健; 海老原秀喜, 日本獣医学会学術集会講演要旨集, 158th, 344, 344, 30 Aug. 2015
(公社)日本獣医学会, Japanese

インフルエンザウイルスのフコシル化α2,3シアロ糖認識機構の解析
日尾野隆大; 岡松正敏; 五十嵐学; 五十嵐学; MCBRIDE Ryan; DE VIRES Robert; PAULSON James; 松野啓太; 松野啓太; 迫田義博; 迫田義博; 喜田宏; 喜田宏; 喜田宏, 日本獣医学会学術集会講演要旨集, 158th, 332, 30 Aug. 2015
Japanese

2014年のベトナムにおける介入有りまたは介入なしの生鳥市場にて単離された鳥インフルエンザウイルスの性状解析(Characterization of avian influenza viruses isolated in live bird markets with and without intervention in Vietnam in 2014)
Chu Duc-Huy; 岡松 正敏; 松野 啓太; 日尾野 隆大; 小笠原 浩平; 鈴木 瑞穂; Nguyen Thanh Lam; 喜田 宏; 迫田 義博, 日本獣医学会学術集会講演要旨集, 158回, 329, 329, Aug. 2015
(公社)日本獣医学会, English

マダニ媒介性フレボウイルスの検出
中尾亮; 梶原将大; 松野啓太; 邱永晋; 森亜紀奈; 海老原秀喜; 高田礼人; 杉本千尋, 大原綜合病院年報, 53, 69, 15 Dec. 2013
Japanese

フィロウイルス糖蛋白質による宿主細胞表面分子の立体的遮蔽現象の解析
野依修; 松野啓太; 梶原将大; 中山絵里; 五十嵐学; 磯田典和; 吉田玲子; 高田礼人, 日本ウイルス学会学術集会プログラム・抄録集, 60th, 198, 31 Oct. 2012
Japanese

Structural characteristic of Ebola viral GP1 involved in attachment and infection.
FUJIHIRA HARUHIKO; USAMI KATSUAKI; DENDA KAORI; YAMADA KEITA; MATSUNO KEITA; SHINOHARA YASURO; TAKADA AYATO; KAKEHI KAZUAKI; IRIMURA TATSURO, 生化学, 84回, ROMBUNNO.3T8A-14, 14, 2011
(公社)日本生化学会, Japanese

Strain-Dependent Glycosylation of Ebola Viral Envelope Glycoproteins Determines their Infectivity
Katsuaki Usami; Haruhiko Fujihira; Kaori Denda-Nagai; Keita Yamada; Keita Matsuno; Ayato Takada; Kazuaki Kakehi; Tatsuro Irimura, GLYCOBIOLOGY, 20, 11, 1529, 1530, Nov. 2010
English, Summary international conference

フィロウイルス種特異抗体検出ELISA法の開発
中山絵里; 横山文香; 宮本洋子; 岸田典子; 松野啓太; 五十嵐学; MARZI Andrea; FELDMANN Heinz; 伊藤公人; 高田礼人, 日本ウイルス学会学術集会プログラム・抄録集, 58th, 286, 15 Oct. 2010
Japanese

マールブルグウイルスの病原性とC型レクチン介在性細胞侵入効率との相関
松野啓太; 岸田典子; 宇佐美克明; 入村達郎; 下島昌幸; 河岡義裕; 高田礼人, 日本ウイルス学会学術集会プログラム・抄録集, 56th, 162, 01 Oct. 2008
Japanese

2008年北海道で発見された斃死オオハクチョウから分離したH5N1高病原性鳥インフルエンザウイルスの性状
岡松正敏; 迫田義博; 吉田裕美; 田中智久; 津田祥美; 磯田典和; 中山絵里; 苫米地大輔; 松野啓太; 梅村孝司; 高田礼人; 喜田宏, 日本ウイルス学会学術集会プログラム・抄録集, 56th, 263, 01 Oct. 2008
Japanese

2008年北海道で発見された斃死オオハクチョウから分離したH5N1高病原性鳥インフルエンザウイルスの性状
岡松正敏; 迫田義博; 吉田裕美; 田中智久; 津田祥美; 磯田典和; 中山絵里; 苫米地大輔; 松野啓太; 梅村孝司; 高田礼人; 喜田宏, 日本獣医学会学術集会講演要旨集, 146th, 193, 05 Sep. 2008
Japanese

Antibody therapy as a future treatment option for Ebola virus infection
Keita Matsuno; Ayato Takada, FUTURE VIROLOGY, 2, 6, 607, 614, Nov. 2007, [Peer-reviewed], [Invited]
English, Book review

ミトゲノム解析によるマダニ系統分類法の開発
中尾亮; 木下豪太; 齋藤歩; 邱永晋; 松野啓太; 杉本千尋; 片倉賢
日本獣医学会学術集会講演要旨集, 30 Aug. 2017, Japanese

2016‐2017年冬季に北日本で野鳥及び飼育鳥から分離されたH5N6高病原性鳥インフルエンザウイルスの性状解析
岡松正敏; 日尾野隆大; 菊谷祐斗; 鈴木瑞穂; NGUYEN Thanh‐Lam; 松野啓太; 松野啓太; 迫田義博; 迫田義博
日本獣医学会学術集会講演要旨集, 30 Aug. 2017, Japanese

Genetic and antigenic characterization of H13 avian influenza viruses(和訳中)
Wang Zu Jyun; 菊谷 祐斗; Nguyen Thanh-Lam; 松野 啓太; 岡松 正敏; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2017, English

Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against a 2.3.4.4 highly pathogenic avian influenza virus(和訳中)
Nguyen Thanh-Lam; 中石 和成; 本島 桂子; 大河原 彩子; 日尾野 隆大; 松野 啓太; 岡松 正敏; 高田 礼人; 喜田 宏; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2017, English

2016-2017年冬季に北日本で野鳥及び飼育鳥から分離されたH5N6高病原性鳥インフルエンザウイルスの性状解析
岡松 正敏; 日尾野 隆大; 菊谷 祐斗; 鈴木 瑞穂; Nguyen Thanh-Lam; 松野 啓太; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2017, Japanese

H13鳥インフルエンザウイルスの遺伝子と抗原の性状(Genetic and antigenic characterization of H13 avian influenza viruses)
Wang Zu Jyun; 菊谷 祐斗; Nguyen Thanh-Lam; 松野 啓太; 岡松 正敏; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2017, English

2.3.4.4高病原性鳥インフルエンザウイルスに対する新規モノクローナル抗体を用いた免疫クロマトグラフィーキットによるH5ヘマグルチニンの迅速かつ広範囲検出(Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit using novel monoclonal antibody against a 2.3.4.4 highly pathogenic avian influenza virus)
Nguyen Thanh-Lam; 中石 和成; 本島 桂子; 大河原 彩子; 日尾野 隆大; 松野 啓太; 岡松 正敏; 高田 礼人; 喜田 宏; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2017, English

マダニとそれに共生するCoxiella属細菌の共進化機構の考察―両者の遺伝的多様性と系統学的位置関係より―
齋藤歩; 中尾亮; THU May June; 邱永晋; 松野啓太; 松野啓太; 杉本千尋; 杉本千尋; 片倉賢
日本獣医学会学術集会講演要旨集, 30 Aug. 2016, Japanese

海外から持ち込まれた未加熱家きん肉から分離された鳥インフルエンザウイルスの性状解析
柴田明弘; 日尾野隆大; 福原久江; 住吉理穂; 大河原彩子; 松野啓太; 松野啓太; 岡松正敏; 迫田義博; 迫田義博; 尾坂優之
日本獣医学会学術集会講演要旨集, 30 Aug. 2016, Japanese

モンゴルにおける豚コレラの発生と分離ウイルスの遺伝子と病原性の解析
迫田義博; 迫田義博; BAZARRAGCHAA Enkhbold; MUNKHDUUREN Shatar; 若森史穂; 日尾野隆大; 松野啓太; 松野啓太; 岡松正敏; BATCHULUUN Damdinjav; 梅村孝司
日本獣医学会学術集会講演要旨集, 30 Aug. 2016, Japanese

ワクチン接種後の鶏におけるH5鳥インフルエンザウイルスの抗原多様性の選択(Selection of antigenic variants of H5 avian influenza viruses in vaccinated chickens)
Nguyen Thanh-Lam; 西 達也; 七戸 新太郎; Chu Duc-Huy; 日尾野 隆大; 松野 啓太; 岡松 正敏; 喜田 宏; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2016, English

北海道で分離された新規ダニ媒介性フレボウイルスの性状解析
鳥居志保; 鳥居志保; 松野啓太; 松野啓太; 中尾亮; 邱永晋; 梶原将大; 直亨則; 村松美笑子; 海老原秀喜; 高田礼人; 高田礼人
日本分子生物学会年会プログラム・要旨集(Web), 2016, Japanese

RT‐PCR法による新規ダニ媒介性フレボウイルス遺伝子の探索
松野啓太; 松野啓太; 下田宙; 鳥居志保; 邱永晋; 中尾亮; 梶原将大; 岡松正敏; 迫田義博; 迫田義博; 奥村敦; 奥村敦; 高田礼人; 高田礼人; 前田健; 海老原秀喜
日本獣医学会学術集会講演要旨集, 30 Aug. 2015, Japanese

インフルエンザウイルスのフコシル化α2,3シアロ糖認識機構の解析
日尾野隆大; 岡松正敏; 五十嵐学; 五十嵐学; MCBRIDE Ryan; DE VIRES Robert; PAULSON James; 松野啓太; 松野啓太; 迫田義博; 迫田義博; 喜田宏; 喜田宏; 喜田宏
日本獣医学会学術集会講演要旨集, 30 Aug. 2015, Japanese

豚コレラウイルス非構造蛋白NS4BのN末端領域の機能解析
田村友和; RUGGLI Nicolas; 松野啓太; 松野啓太; 岡松正敏; 迫田義博; 迫田義博
日本獣医学会学術集会講演要旨集, 30 Aug. 2015, Japanese

2014年のベトナムにおける介入有りまたは介入なしの生鳥市場にて単離された鳥インフルエンザウイルスの性状解析(Characterization of avian influenza viruses isolated in live bird markets with and without intervention in Vietnam in 2014)
Chu Duc-Huy; 岡松 正敏; 松野 啓太; 日尾野 隆大; 小笠原 浩平; 鈴木 瑞穂; Nguyen Thanh Lam; 喜田 宏; 迫田 義博
日本獣医学会学術集会講演要旨集, Aug. 2015, English

エボラウイルス表層糖タンパク質に対する糖鎖修飾制御メカニズムの解明
藤平 陽彦; 宇佐美 克明; 伝田 香里; 松野 啓太; 篠原 康郎; 佐藤 あやの; 高田 礼人; 入村 達郎
日本生化学会大会プログラム・講演要旨集, Dec. 2012, Japanese

フィロウイルス糖蛋白質による宿主細胞表面分子の立体的遮蔽現象の解析
野依修; 松野啓太; 梶原将大; 中山絵里; 五十嵐学; 磯田典和; 吉田玲子; 高田礼人
日本ウイルス学会学術集会プログラム・抄録集, 31 Oct. 2012, Japanese

抗体によるマールブルグウイルスの出芽阻害
梶原将大; MARZI Andrea; 中山絵里; 野田岳志; 黒田誠; RASHID Manzoor; 松野啓太; FELDMANN Heinz; 吉田玲子; 河岡義裕; 高田礼人
日本獣医学会学術集会講演要旨集, 31 Aug. 2012, Japanese

感染症学特別研究Ⅰ, 2024年, 博士後期課程, 国際感染症学院

越境性感染症学特論, 2024年, 博士後期課程, 国際感染症学院

Promotion of comprehensive interdisciplinary virology for the post-COVID era
Grants-in-Aid for Scientific Research
17 Nov. 2023 - 31 Mar. 2030
佐藤 佳; 福原 崇介; 松野 啓太; 齊藤 暁; 木村 香菜子
Japan Society for the Promotion of Science, Fund for the Promotion of Joint International Research (International Leading Research ), The University of Tokyo, 23K20041

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

Molecular basis of the emerging nairovirus infections
Grants-in-Aid for Scientific Research
01 Apr. 2023 - 31 Mar. 2027
松野 啓太; 谷 英樹; 山口 宏樹
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K27066

フィロウイルスに広く効果を示すユニバーサル治療薬探索のための基盤技術の確立
科学研究費助成事業
01 Apr. 2023 - 31 Mar. 2026
五十嵐 学; 広川 貴次; 阿部 貴志; 松野 啓太
フィロウイルスに含まれるエボラおよびマールブルグウイルスは、ヒトに致死的な出血熱を引き起こす。その発生頻度は近年増加傾向にあり、原因ウイルス種も予測不能である。そのため、フィロウイルスに広く対応可能な治療薬開発が望まれている。しかし、感染性フィロウイルスはBSL-4施設を備えた限られた機関でしか扱えず、治療薬探索には工夫が必要である。そこで本研究では、計算機解析を活用し、ウイルス蛋白質の配列と構造情報から、フィロウイルス種に共通する創薬標的部位を同定する技術を確立する。また、同定した標的部位に対する阻害剤を設計・探索し、フィロウイルス種に広く効果を示す化合物を見つけ出す。
ウイルスの増殖過程において、個々のウイルス蛋白質は、ウイルス蛋白質同士あるいは宿主分子と相互作用することで機能を発揮する。したがって、ウイルス蛋白質上の相互作用および機能に関連する部位（相互作用/機能部位）は、近縁ウイルス間で保存されている可能性が高い。このような部位は、フィロウイルスに幅広く効果を示す薬剤の標的になる可能性がある。本年度は、深層学習モデル Transformer を用いて、ウイルスのアミノ酸配列から蛋白質間相互作用に重要なモチーフ（Short Linear Motif: SLiM）を検出する手法の開発を行った。また、エボラおよびマールブルグウイルスの表面糖蛋白GPとエンドソーム受容体であるNiemann-Pick C1（NPC1）蛋白質との複合体構造を分子シミュレーションにより解析し、GP上のNPC1結合領域が両ウイルス共通の創薬標的部位となり得るかを検証した。
日本学術振興会, 基盤研究(B), 北海道大学, 23K27064

宿主RNAメチルトランスフェラーゼを標的とした抗インフルエンザウイルス薬の探索
科学研究費助成事業 国際共同研究加速基金(国際共同研究強化(B))
07 Oct. 2022 - 31 Mar. 2026
五十嵐 学; 松野 啓太; 日尾野 隆大
日本学術振興会, 国際共同研究加速基金(国際共同研究強化(B)), 北海道大学, 22KK0094

イバラキウイルス感染における相補現象の分子基盤とウイルス生存戦略
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
松尾 栄子; 松野 啓太
日本学術振興会, 基盤研究(C), 神戸大学, 22K05986

汎フィロウイルス治療薬開発に向けたドライ-ウェット融合型研究基盤の構築
科学研究費助成事業
01 Apr. 2020 - 31 Mar. 2023
五十嵐 学; 広川 貴次; 阿部 貴志; 松野 啓太
日本学術振興会, 基盤研究(B), 北海道大学, 20H03140

Global profiling of pathogens in ticks
Grants-in-Aid for Scientific Research
01 Apr. 2019 - 31 Mar. 2023
松野 啓太; 山口 宏樹; 大場 靖子; 梶原 将大
本年度は主に、昨年度までに検出あるいは分離培養に成功したマダニ由来ウイルスについての性状解析を実施した。さらに、昨年度に報告したマダニ咬傷後に発熱を呈した患者から検出されたオルソナイロウイルス（Yezoウイルス)が分布していると考え られる北海道において、このウイルスを対象とした性状解析ならびに野外調査を実施した。なお、Yezoウイルスの調査については、他研究費との連携により効率的に展開した。また、マダニからオルソナイロウイルスを検出する系を樹立し、実際に北海道のマダニから複数のオルソナイロウイルスを検出した。本年度は新型コロナウ イルス感染拡大の影響で、海外でのマダニ採集が引き続き困難になったため、研究協力者からマダニを送付してもらうなどの代替策を進め、採集地域が限定されることを防いだ。さらに、実験室内で人為的にウイルスを接種したマダニを用いた実験モデルからのウイルス検出・分離培養方法検証を進め、状況が改善した際に野外調査を精力的に進められるよう準備を行った。 マダニから分離培養された各微生物については、遺伝情報解読と病原性解析の2つの性状比較解析を実施し、マダニから検出された各微生物は、サンガーシークエンサーと次世代シークエンサーを併用して遺伝子配列を解読した。さらに、これまでに収集あるいは分離培養したウイルスについて、実験動物を用いて病原性の検討を実施した。これらの結果を用いて、微生物のプロファイリングに用いることができる基礎的データを収集し、各微生物について塩基配列およびアミノ酸配列に基づいて病原性を推定する方法の検討を開始した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H03112

Searching for core-network of host factors regulating virus infections by comparing vertebrate and arthropod responses
Grants-in-Aid for Scientific Research
18 Jul. 2017 - 31 Mar. 2021
Matsuno Keita
Infectious diseases caused by arboviruses (viruses transmitted by blood-sucking arthropods and can also grow in the arthropods), such as dengue fever and SFTS, have become a severe problem on public health worldwide. A common feature of arboviruses is that they can grow in both vertebrates and arthropods. In this study, we compared host factor networks between vertebrates and arthropods, and extracted a homologous core network. We then identified several host factors that are likely to be associated with arbovirus replication in cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17KT0045

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

Screening of novel tick-borne phlebovirus and virulence factor of SFTS virus
Grants-in-Aid for Scientific Research
01 Apr. 2016 - 31 Mar. 2019
MATSUNO Keita; Kajihara Masahiro; Ebihara Hideki
Sever fever with thrombocytopenia syndrome (SFTS) virus causes fatal febrile illness in humans and has obtained lots of attention in Eastern Asia, including Japan. In the present study, the present study aims to reveal the evolutional process in which SFTS virus increases its virulence to humans by comparing tick-borne phleboviruses closely related to SFTS virus. Novel tick-borne phleboviruses were identified in Japan and also in abroad, and wild animals were suggested to be infected with these viruses. Tick-borne phleboviruses seem to coevolve with ticks, and acquisition of NSs gene could be associated with SFTS virus virulence.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, 16K18791

新規ダニ媒介性フレボウイルスの探索と性状解析
科学研究費助成事業
28 Aug. 2015 - 31 Mar. 2016
松野 啓太
北海道を中心とした日本国内各地、ならびに海外各地において、マダニを採集しフレボウイルス遺伝子のスクリーニングを行った。合計4属10種約2千匹のマダニより、プールを含む94検体中でフレボウイルス遺伝子を検出した。検出されたフレボウイルス遺伝子の塩基配列を系統解析したところ、日本のマダニから検出されたフレボウイルス遺伝子は11群の、海外2カ国のマダニから検出されたウイルスはそれぞれ独立した群を形成し、SFTSウイルスとは遺伝的に大きく離れていた。日本の5群は既存のどのフレボウイルス種とも系統的に異なり、新規フレボウイルスである可能性が示唆された。本研究では、日本国内外のマダニからフレボウイルス遺伝子を検出し、マダニ中には、これまで知られている以上に多様なフレボウイルスが存在する可能性を明らかにした。フレボウイルス遺伝子が検出されたマダニ乳剤を培養細胞に接種し、ウイルス分離を試みたところ、日本の限定された地域で採集されたシュルツェマダニからのみ検出される互いに近縁な2種の新規フレボウイルスの分離に成功した。これらのウイルスの遺伝子全長配列を次世代シークエンサーにより決定したところ、マダニ由来フレボウイルスのいずれともまったく異なる新しい系統に属することが分かった。さらに、このウイルスをC57BL/6マウスに皮下接種したところ、感染3日後に脾臓でのウイルス増殖が確認され、哺乳動物での増殖性を有していることが明らかになった。
日本学術振興会, 研究活動スタート支援, 北海道大学, 15H05992

フィロウイルス感染症の予防・制圧に向けた基礎研究
科学研究費助成事業
2008 - 2010
松野 啓太
これまで、本研究によってマールブルグウイルス株間のC型レクチン介在性細胞侵入効率は表面糖タンパク質GP上の547番目のアミノ酸によって決まり、このアミノ酸はC型レクチン介在性細胞侵入の際に、GPのcathepsin感受性を決める因子である可能性が示された。このアミノ酸の違いによるウイルス感染効率の差は、C型レクチンを強制発現させた細胞でのみ観察され、マールブルグウイルスのC型レクチン介在性細胞侵入では、本来の細胞侵入機構と異なる仕組みによってウイルスの細胞侵入効率が制御されているかもしれない。
フィロウイルスは通常、GP上のレセプター結合領域と細胞表面の未同定の宿主因子との結合によって細胞に吸着し、細胞内に侵入すると考えられる。一方で、C型レクチンはGP上の糖鎖を認識するため、レセプター結合領域以外の領域とも結合できる。そこで、本研究では、レセプター結合領域に変異を加えてその機能を欠損させ、C型レクチン介在性の細胞侵入が起きるかどうかを検討した。レセプター結合領域に変異を加えたGPをまとったシュードタイプウイルスは、野生型GPを持つウイルスが効率良く感染するVero細胞などへの感染性が低下した。さらに、C型レクチン強制発現細胞においても、これらの変異GPを持つウイルスの感染性は同様に低下し、C型レクチンの存在により感染性が回復することはなかった。したがって、C型レクチンとGPとの結合はフィロウイルス感染を担うことはできず、その役割は限定的であると考えられる。
日本学術振興会, 特別研究員奨励費, 北海道大学, 08J03378