2023/10/19 更新

写真a

マツモト ユウスケ
松本 祐介
MATSUMOTO Yuusuke
所属
農水産獣医学域獣医学系 共同獣医学部 附属越境性動物疾病制御研究センター 准教授
職名
准教授

研究キーワード

  • ウイルス学

研究分野

  • ライフサイエンス / ウイルス学

  • ライフサイエンス / 分子生物学

  • ライフサイエンス / 獣医学

学歴

  • 大阪大学   大学院医学系研究科

    2009年4月 - 2012年9月

  • 京都大学   ウイルス研究所   ヒトがんウイルス研究分野

    2011年4月 - 2012年9月

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    備考: 特別研究学生

  • 宮崎大学   農学部   獣医学科

    2003年4月 - 2009年3月

経歴

  • 鹿児島大学   農水産獣医学域獣医学系 共同獣医学部附属越境性動物疾病制御研究センター 附属越境性動物疾病制御研究センター   准教授

    2022年10月 - 現在

  • 鹿児島大学   共同獣医学部 附属越境性動物疾病制御研究センター   准教授

    2022年10月 - 現在

  • 公益財団法人東京都医学総合研究所   感染制御プロジェクト   主任研究員

    2020年9月 - 2022年9月

  • 和歌山県立医科大学   医学部 微生物学教室   助教

    2014年4月 - 2020年8月

  • 京都大学   ウイルス研究所 ヒトがんウイルス研究分野   博士研究員

    2013年11月 - 2014年3月

  • Case Western Reserve University   Department of Molecular Biology & Microbiology   Post Doctoral Scholar

    2013年7月 - 2013年10月

  • Cleveland Clinic   Lerner Research Institute   Post Doctoral Fellow

    2012年10月 - 2013年6月

▼全件表示

所属学協会

  • 日本獣医学会

    2022年10月 - 現在

  • 日本RNA学会

    2022年6月 - 現在

  • 日本ウイルス学会

    2008年8月 - 現在

 

論文

  • Sakiko Toyama, Tomoko Honda, Sadahiro Iwabuchi, Shinichi Hashimoto, Kenzaburo Yamaji, Yuko Tokunaga, Yusuke Matsumoto, Hideya Kawaji, Takashi Miyazaki, Yoshiaki Kikkawa, Michinori Kohara .  Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination. .  Frontiers in immunology14   1209945 - 1209945   2023年招待 査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3-6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3-6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3-6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3-6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3-6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.

    DOI: 10.3389/fimmu.2023.1209945

    PubMed

  • Hirohito Ishigaki, Fumihiko Yasui, Misako Nakayama, Akinori Endo, Naoki Yamamoto, Kenzaburo Yamaji, Cong Thanh Nguyen, Yoshinori Kitagawa, Takahiro Sanada, Tomoko Honda, Tsubasa Munakata, Masahiko Higa, Sakiko Toyama, Risa Kono, Asako Takagi, Yusuke Matsumoto, Aya Koseki, Kaori Hayashi, Masanori Shiohara, Koji Ishii, Yasushi Saeki, Yasushi Itoh, Michinori Kohara .  An attenuated vaccinia vaccine encoding the severe acute respiratory syndrome coronavirus-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human angiotensin-converting enzyme 2 transgenic mice from severe acute respiratory syndrome coronavirus-2 and its variants .  Frontiers in Microbiology13   967019   2022年11月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    As long as the coronavirus disease-2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently required. We have developed a vaccine consisting of the attenuated vaccinia virus Dairen-I (DIs) strain platform carrying the SARS-CoV-2  S gene (rDIs-S). rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin-converting enzyme 2 (hACE2) transgenic mice, and the mouse model showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-873). Using a tandem mass tag (TMT)-based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that vaccination with rDIs-S maintains S protein-specific antibody titers for at least 6 months after a first vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current variants such as Omicron BA.1 and possibly future variants.

    DOI: 10.3389/fmicb.2022.967019

  • Yutaro Neriya, Shohei Kojima, Arata Sakiyama, Mai Kishimoto, Takao Iketani, Tadashi Watanabe, Yuichi Abe, Hiroshi Shimoda, Keisuke Nakagawa, Takaaki Koma, Yusuke Matsumoto .  A comprehensive list of the Bunyavirales replication promoters reveals a unique promoter structure in Nairoviridae differing from other virus families. .  Scientific reports12 ( 1 ) 13560 - 13560   2022年8月招待 査読 国際誌

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Members of the order Bunyavirales infect a wide variety of host species, including plants, animals and humans, and pose a threat to public health. Major families in this order have tri-segmented negative-sense RNA genomes, the 5' and 3' ends of which form complementary strands that serve as a replication promoter. Elucidation of the mechanisms by which viral polymerases recognize the promoter to initiate RNA synthesis is important for understanding viral replication and pathogenesis, and developing antivirals. A list of replication promoter configuration patterns may provide details on the differences in the replication mechanisms among bunyaviruses. By using public sequence data of all known bunyavirus species, we constructed a comprehensive list of the replication promoters comprising 40 nucleotides in both the 5' and 3' ends of the genome that form a specific complementary strand. Among tri-segmented bunyaviruses, members of the family Nairoviridae, including the highly pathogenic Crimean-Congo hemorrhagic fever virus, have evolved a GC-rich promoter structure differing from that of other families. The unique promoter structure might be related to the large genome size of the family Nairoviridae among bunyaviruses, and the large genome architecture might confer pathogenic advantages. The promoter list provided in this report is useful for predicting the virus family-specific replication mechanisms of bunyaviruses.

    DOI: 10.1038/s41598-022-17758-z

    PubMed

  • Hirohito Ishigaki, Fumihiko Yasui, Misako Nakayama, Akinori Endo, Naoki Yamamoto, Kenzaburo Yamaji, Cong Thanh Nguyen, Yoshinori Kitagawa, Takahiro Sanada, Tomoko Honda, Tsubasa Munakata, Masahiko Higa, Sakiko Toyama, Risa Kono, Asako Takagi, Yusuke Matsumoto, Kaori Hayashi, Masanori Shiohara, Koji Ishii, Yasushi Saeki, Yasushi Itoh, Michinori Kohara .  An attenuated vaccinia vaccine encoding the SARS-CoV-2 spike protein elicits broad and durable immune responses, and protects cynomolgus macaques and human ACE2 transgenic mice from SARS-CoV-2 and its variants .      2022年6月

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    記述言語:英語  

    DOI: 10.1101/2022.06.12.495779

  • Fumihiko Yasui, Yusuke Matsumoto, Naoki Yamamoto, Takahiro Sanada, Tomoko Honda, Tsubasa Munakata, Yasushi Itoh, Michinori Kohara .  Infection with the SARS-CoV-2 B.1.351 variant is lethal in aged BALB/c mice. .  Scientific reports12 ( 1 ) 4150 - 4150   2022年3月招待 査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Models of animals that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can usefully evaluate the efficacy of vaccines and therapeutics. In this study, we demonstrate that infection with the SARS-CoV-2 B.1.351 variant (TY8-612 strain) induces bodyweight loss and inflammatory cytokine/chemokine production in wild-type laboratory mice (BALB/c and C57BL/6 J mice). Furthermore, compared to their counterparts, BALB/c mice had a higher viral load in their lungs and worse symptoms. Importantly, infecting aged BALB/c mice (older than 6 months) with the TY8-612 strain elicited a massive and sustained production of multiple pro-inflammatory cytokines/chemokines and led to universal mortality. These results indicated that the SARS-CoV-2 B.1.351 variant-infected mice exhibited symptoms ranging from mild to fatal depending on their strain and age. Our data provide insights into the pathogenesis of SARS-CoV-2 and may be useful in developing prophylactics and therapeutics.

    DOI: 10.1038/s41598-022-08104-4

    PubMed

  • Naoki Saka, Yusuke Matsumoto, Keisuke Ohta, Daniel Kolakofsky, Machiko Nishio .  A Point Mutation in the Human Parainfluenza Virus Type 2 Nucleoprotein Leads to Two Separate Effects on Virus Replication. .  Journal of virology96 ( 4 ) e0206721   2022年2月招待 査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Paramyxovirus genomes, like that of human parainfluenza virus type 2 (hPIV2), have lengths of precisely multiples-of-six nucleotides ("rule of six"), where each nucleoprotein subunit (NP) binds exactly six nucleotides. Ten residues of its RNA binding groove contact the genome RNA; but only one, Q202, directly contacts a nucleotide base. The mutation of NPQ202 leads to two phenotypes: the ability of the viral polymerase to replicate minigenomes with defective bipartite promoters where NPwt is inactive, and the inability to rescue rPIV2 carrying this point mutation by standard means. The absence of an rPIV2 NPQ202A prevented further study of the latter phenotype. By extensive and repeated cocultivation of transfected cells, an rPIV2 carrying this mutation was finally recovered, and this virus was apparently viable due to the presence of an additional NP mutation (I35L). Our results suggest that these two phenotypes are due to separate effects of the Q202 mutation, and that the problematic rescue phenotype may be due to the inability of the transfected cell to incorporate viral nucleocapsids during virus budding. IMPORTANCE Paramyxovirus genomes are contained within a noncovalent homopolymer of its nucleoprotein (NP) and form helical nucleocapsids (NC) whose 3' ends contain the promoters for the initiation of viral RNA synthesis. This work suggests that these NC 3' ends may play another role in the virus life cycle via their specific interaction with virus-modified cell membranes needed for the incorporation of viral NCs into budding virions.

    DOI: 10.1128/JVI.02067-21

    PubMed

  • Takahiro Sanada, Tomoko Honda, Fumihiko Yasui, Kenzaburo Yamaji, Tsubasa Munakata, Naoki Yamamoto, Makoto Kurano, Yusuke Matsumoto, Risa Kohno, Sakiko Toyama, Yoshiro Kishi, Takuro Horibe, Yudai Kaneko, Mayumi Kakegawa, Kazushige Fukui, Takeshi Kawamura, Wang Daming, Chungen Qian, Fuzhen Xia, Fan He, Syudo Yamasaki, Atsushi Nishida, Takayuki Harada, Masahiko Higa, Yuko Tokunaga, Asako Takagi, Masanari Itokawa, Tatsuhiko Kodama, Michinori Kohara .  Serologic Survey of IgG Against SARS-CoV-2 Among Hospital Visitors Without a History of SARS-CoV-2 Infection in Tokyo, 2020-2021. .  Journal of epidemiology32 ( 2 ) 105 - 111   2022年2月招待 査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Tokyo, the capital of Japan, is a densely populated city of >13 million people, so the population is at high risk of epidemic severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. A serologic survey of anti-SARS-CoV-2 IgG would provide valuable data for assessing the city's SARS-CoV-2 infection status. Therefore, this cross-sectional study estimated the anti-SARS-CoV-2 IgG seroprevalence in Tokyo. METHODS: Leftover serum of 23,234 hospital visitors was tested for antibodies against SARS-CoV-2 using an iFlash 3000 chemiluminescence immunoassay analyzer (Shenzhen YHLO Biotech, Shenzhen, China) with an iFlash-SARS-CoV-2 IgG kit (YHLO) and iFlash-SARS-CoV-2 IgG-S1 kit (YHLO). Serum samples with a positive result (≥10 AU/mL) in either of these assays were considered seropositive for anti-SARS-CoV-2 IgG. Participants were randomly selected from patients visiting 14 Tokyo hospitals between September 1, 2020 and March 31, 2021. No participants were diagnosed with coronavirus disease 2019 (COVID-19), and none exhibited COVID-19-related symptoms at the time of blood collection. RESULTS: The overall anti-SARS-CoV-2 IgG seroprevalence among all participants was 1.83% (95% confidence interval [CI], 1.66-2.01%). The seroprevalence in March 2021, the most recent month of this study, was 2.70% (95% CI, 2.16-3.34%). After adjusting for population age, sex, and region, the estimated seroprevalence in Tokyo was 3.40%, indicating that 470,778 individuals had a history of SARS-CoV-2 infection. CONCLUSIONS: The estimated number of individuals in Tokyo with a history of SARS-CoV-2 infection was 3.9-fold higher than the number of confirmed cases. Our study enhances understanding of the SARS-CoV-2 epidemic in Tokyo.

    DOI: 10.2188/jea.JE20210324

    PubMed

  • Keisuke Ohta, Yusuke Matsumoto, Machiko Nishio .  Common and unique mechanisms of filamentous actin formation by viruses of the genus Orthorubulavirus. .  Archives of virology165 ( 4 ) 799 - 807   2020年4月招待 査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We previously found that infection with human parainfluenza virus type 2 (hPIV-2), a member of the genus Orthorubulavirus, family Paramyxoviridae, causes filamentous actin (F-actin) formation to promote viral growth. In the present study, we investigated whether similar regulation of F-actin formation is observed in infections with other rubulaviruses, such as parainfluenza virus type 5 (PIV-5) and simian virus 41 (SV41). Infection with these viruses caused F-actin formation and RhoA activation, which promoted viral growth. These results indicate that RhoA-induced F-actin formation is important for efficient growth of these rubulaviruses. Only SV41 and hPIV-2 V and P proteins bound to Graf1, while the V and P proteins of PIV-5, mumps virus, and hPIV-4 did not bind to Graf1. In contrast, the V proteins of these rubulaviruses bound to both inactive RhoA and profilin 2. These results suggest that there are common and unique mechanisms involved in regulation of F-actin formation by members of the genus Orthorubulavirus.

    DOI: 10.1007/s00705-020-04565-y

    PubMed

  • Keisuke Ohta, Yusuke Matsumoto, Machiko Nishio .  Inhibition of Cavin3 Degradation by the Human Parainfluenza Virus Type 2 V Protein Is Important for Efficient Viral Growth. .  Frontiers in microbiology11   803 - 803   2020年招待 査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cavin proteins have important roles in the formation of caveolae in lipid raft microdomains. Pulse-chase experiments of cells infected with human parainfluenza virus type 2 (hPIV-2) showed decreased proteasomal degradation of Cavin3. Overexpression of hPIV-2 V protein alone was sufficient to inhibit Cavin3 degradation. Immunoprecipitation analysis revealed that V protein bound to Cavin3. Trp residues within C-terminal region of V protein, as well as the N-terminal region of Cavin3, are important for V-Cavin3 interaction. Cavin3 knockdown suppressed hPIV-2 growth without affecting its entry, replication, transcription, or translation. Higher amounts of Cavin3 were observed in V protein-overexpressing cells than in control cells in lipid raft microdomains. Our data collectively suggest that hPIV-2 V protein binds to and stabilizes Cavin3, which in turn facilitates assembly and budding of hPIV-2 in lipid raft microdomains.

    DOI: 10.3389/fmicb.2020.00803

    PubMed

  • Keisuke Ohta, Yusuke Matsumoto, Machiko Nishio .  Profilin2 is required for filamentous actin formation induced by human parainfluenza virus type 2. .  Virology533   108 - 114   2019年7月招待 査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We previously reported that human parainfluenza virus type 2 (hPIV-2) promoted RhoA activation and subsequent filamentous actin (F-actin) formation. Actin-binding proteins, such as profilin and cofilin, are involved in the regulation of F-actin formation by RhoA signaling. In the present study, we identified profilin2 as a key molecule that is involved in hPIV-2-induced F-actin formation. Immunoprecipitation assays demonstrated that hPIV-2 V protein binds to profilin2 but not to profilin1. Mutation of Trp residues within C-terminal region of V protein abolished the binding capacity to profilin2. Depletion of profilin2 resulted in the inhibition of hPIV-2-induced F-actin formation and the suppression of hPIV-2 growth. Overexpression of wild type V but not Trp-mutated V protein reduced the quantity of actin co-immunoprecipitated with profilin2. Taken together, these results suggest that hPIV-2 V protein promotes F-actin formation by affecting actin-profilin2 interaction through its binding to profilin2.

    DOI: 10.1016/j.virol.2019.05.013

    PubMed

  • Matsumoto Y, Ohta K, Nishio M .  Importance of tyrosine in the RNA-binding domain of human parainfluenza virus type 2 nucleoprotein for polymerase activity. .  Archives of virology164 ( 7 ) 1851 - 1855   2019年5月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00705-019-04240-x

    PubMed

  • Yumine N, Matsumoto Y, Ohta K, Fukasawa M, Nishio M .  Claudin-1 inhibits human parainfluenza virus type 2 dissemination. .  Virology531   93 - 99   2019年5月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.virol.2019.01.031

    PubMed

  • Matsumoto Y, Nouchi T, Ohta K, Nishio M .  Regulation of Hazara virus growth through apoptosis inhibition by viral nucleoprotein. .  Archives of virology164 ( 6 ) 1597 - 1607   2019年4月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00705-019-04236-7

    PubMed

  • Matsumoto Y, Ohta K, Kolakofsky D, Nishio M .  A Minigenome Study of Hazara Nairovirus Genomic Promoters. .  Journal of virology93 ( 6 )   2019年3月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1128/JVI.02118-18

    PubMed

  • Ohtsuka J, Matsumoto Y, Ohta K, Fukumura M, Tsurudome M, Nosaka T, Nishio M .  Nucleocytoplasmic shuttling of the human parainfluenza virus type 2 phosphoprotein. .  Virology528   54 - 63   2019年2月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.virol.2018.12.005

    PubMed

  • Ohta K, Matsumoto Y, Yumine N, Nishio M .  The V protein of human parainfluenza virus type 2 promotes RhoA-induced filamentous actin formation. .  Virology524   90 - 96   2018年11月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.virol.2018.08.015

    PubMed

  • Keisuke Ohta, Yusuke Matsumoto, Machiko Nishio .  Rab27a facilitates human parainfluenza virus type 2 growth by promoting cell surface transport of envelope proteins .  Medical Microbiology and Immunology207 ( 2 ) 141 - 150   2018年4月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Verlag  

    Human parainfluenza virus type 2 (hPIV-2) proteins and genomes newly synthesized in the cytoplasm need to be transported to the plasma membrane where budding occurs. This mechanism, where Rab proteins regulate intracellular traffic by switching between GTP-bound active form and GDP-bound inactive form, is not fully understood. mRNA and protein expression levels of Rab8a, Rab11a, and Rab27a are not altered by hPIV-2 infection. hPIV-2 growth is affected by depletion of Rab27a but not Rab8a and Rab11a. Overexpression of a constitutively active mutant of Rab27a Q78L promotes the cell surface levels of fusion (F) and hemagglutinin-neuraminidase (HN) proteins in hPIV-2-infected cells without affecting viral mRNA levels. Increase in the cell surface level of F and HN proteins by Rab27a Q78L is noticeable when these proteins are coexpressed independent of hPIV-2 infection. Our results collectively suggest that the active form of Rab27a enhances hPIV-2 growth by promoting transport of F and HN proteins to the plasma membrane.

    DOI: 10.1007/s00430-018-0536-3

    Scopus

    PubMed

  • Yusuke Matsumoto, Keisuke Ohta, Daniel Kolakofsky, Machiko Nishio .  The control of paramyxovirus genome hexamer length and mRNA editing .  RNA24 ( 4 ) 461 - 467   2018年4月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cold Spring Harbor Laboratory Press  

    The unusual ability of a human parainfluenza virus type 2 (hPIV2) nucleoprotein point mutation (NPQ202A) to strongly enhance minigenome replication was found to depend on the absence of a functional, internal element of the bipartite replication promoter (CRII). This point mutation allows relatively robust CRII-minus minigenome replication in a CRII-independent manner, under conditions in which NPwt is essentially inactive. The nature of the amino acid at position 202 apparently controls whether viral RNA-dependent RNA polymerase (vRdRp) can, or cannot, initiate RNA synthesis in a CRII-independent manner. By repressing genome synthesis when vRdRp cannot correctly interact with CRII, gln202 of N, the only residue of the RNA-binding groove that contacts a nucleotide base in the N-RNA, acts as a gatekeeper for wild-type (CRII-dependent) RNA synthesis. This ensures that only hexamer-length genomes are replicated, and that the critical hexamer phase of the cis-acting mRNA editing sequence is maintained.

    DOI: 10.1261/rna.065243.117

    Scopus

    PubMed

  • Keisuke Ohta, Yusuke Matsumoto, Machiko Nishio .  Human parainfluenza virus type 2 V protein inhibits caspase-1 .  Journal of General Virology99 ( 4 ) 501 - 511   2018年4月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Microbiology Society  

    The multifunctional V protein of human parainfluenza virus type 2 (hPIV2) plays important roles in controlling viral genome replication, inhibiting the host interferon response and promoting virus growth. We screened a yeast two-hybrid library using V protein as bait to identify host factors that are important for other functions of V. One of several positive clones isolated from HeLa cell-derived cDNA library encodes caspase-1. We found that the C-terminal region of V interacts with the C-terminal region of caspase-1 in mammalian cells. Moreover, the V protein repressed caspase-1 activity and the formation of interleukin1β (IL-1 β) in a dose-dependent manner. IL-1 β secretion induced by wild-type hPIV2 infection in human monocytic THP-1 cells was significantly lower than that induced by recombinant hPIV2 lacking V protein or having a mutant V. These data suggest that hPIV2 V protein inhibits caspase-1-mediated maturation of IL-1 β via its interaction with caspase-1.

    DOI: 10.1099/jgv.0.001037

    Scopus

    PubMed

  • Yusuke Matsumoto, Keisuke Ohta, Machiko Nishio .  Lethal infection of embryonated chicken eggs by Hazara virus, a model for Crimean-Congo hemorrhagic fever virus .  Archives of Virology163 ( 1 ) 219 - 222   2018年1月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer-Verlag Wien  

    Hazara virus (HAZV) is a member of the genus Orthonairovirus of the family Nairoviridae. HAZV is closely related to Crimean-Congo hemorrhagic fever virus but differs in that it is non-pathogenic to humans. To establish an infection model system, we tested whether embryonated chicken eggs, which are classically used for evaluating viral pathogenicity, are susceptible to HAZV infection. We demonstrated that HAZV replicates well in embryonated chicken eggs and kills 100% of the embryos. This can be a valuable tool to evaluate the lethality of nairoviruses in a biosafety level 2 laboratory.

    DOI: 10.1007/s00705-017-3580-1

    Scopus

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  • Yusuke Matsumoto, Keisuke Ohta, Machiko Nishio .  Human parainfluenza virus type 2 polymerase complex recognizes leader promoters of other species belonging to the genus Rubulavirus .  MEDICAL MICROBIOLOGY AND IMMUNOLOGY206 ( 6 ) 441 - 446   2017年12月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Leader sequence, located at the 3' terminus of paramyxovirus genomes, determines the degree of viral transcription and replication. The essential nucleotides in the leader sequence that influence viral propagation, however, have not been investigated in detail. In the present study, we show that polymerase complex of human parainfluenza virus type 2 (hPIV2) uses a luciferase-encoding hPIV2 mini-genome possessing the leader sequence from other closely related viruses as a template. Furthermore, we demonstrate that although hPIV2 polymerase complex can recognize the leader sequence of hPIV4B, mumps virus (MuV) and PIV5 as well as Newcastle disease virus (NDV), it cannot recognize measles virus, hPIV1, Sendai virus (SeV) or hPIV3. We could obtain the chimeric hPIV2 possessing the leader sequence from hPIV4B, MuV and PIV5, but not from other species, including NDV and SeV. These results reveal that although hPIV2 polymerase complex can recognize the leader sequence from rubulaviruses to achieve efficient viral infection, this does not apply to viruses belonging to other genus. A comparison of leader sequence nucleotides among paramyxoviruses highlights the importance of the conservation in the first 13 nucleotides for infectious hPIV2 growth.

    DOI: 10.1007/s00430-017-0520-3

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  • Keisuke Ohta, Yusuke Matsumoto, Morihiro Ito, Machiko Nishio .  Tetherin antagonism by V proteins is a common trait among the genus Rubulavirus .  MEDICAL MICROBIOLOGY AND IMMUNOLOGY206 ( 4 ) 319 - 326   2017年8月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Tetherin (BST-2/CD317/HM1.24) is an anti-viral factor that restricts the budding of several enveloped viruses. Most of these viruses have evolved to encode tetherin antagonists. Our previous study demonstrated that the growth of human parainfluenza virus type 2 (hPIV-2), a member of the genus Rubulavirus in the family Paramyxoviridae, was inhibited by tetherin, and its V protein decreases the amount of cell surface tetherin by the interaction. In the present study, we investigated whether tetherin inhibits the growth of other rubulaviruses including PIV-5, mumps virus (MuV), simian virus 41, and hPIV-4, and whether their V proteins act as tetherin antagonists. Plaque assay demonstrated that the growth of PIV-5 and MuV was inhibited by tetherin. Flow cytometry and immunoblot analyses revealed that the infection of PIV-5 and MuV caused reduction of cell surface tetherin without affecting total amount of tetherin. Immunoprecipitation analysis showed that all V proteins of rubulaviruses tested bound to tetherin. These results suggest that tetherin antagonism by V proteins is common among the genus Rubulavirus.

    DOI: 10.1007/s00430-017-0509-y

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  • Ohta K, Matsumoto Y, Yumine N, Nishio M .  Human parainfluenza virus type 2 V protein inhibits induction of tetherin. .  Medical microbiology and immunology206 ( 4 ) 311 - 318   2017年8月査読 国際誌

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00430-017-0508-z

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  • Yusuke Matsumoto, Keisuke Ohta, Daniel Kolakofsky, Machiko Nishio .  A Point Mutation in the RNA-Binding Domain of Human Parainfluenza Virus Type 2 Nucleoprotein Elicits Abnormally Enhanced Polymerase Activity .  JOURNAL OF VIROLOGY91 ( 9 )   2017年5月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    The genome RNA of human parainfluenza virus type 2 (hPIV2) that acts as the template for the polymerase complex is entirely encapsidated by the nucleoprotein (NP). Recently, the crystal structure of NP of PIV5, a virus closely related to hPIV2, was resolved in association with RNA. Ten amino acids that contact the bound RNA were identified and are strictly conserved between PIV5 and hPIV2 NP. Mutation of hPIV2 NP Q202 (which contacts a base rather than the RNA backbone) to various amino acids resulted in an over 30-fold increase of polymerase activity as evidenced by a minireplicon assay, even though the RNA-binding affinity was unaltered. Using various modified minireplicons, we found that the enhanced reporter gene expression could be accounted for by increased minigenome replication, whereas mRNA synthesis itself was not affected by Q202 mutation. Moreover, the enhanced activities were still observed in minigenomes partially lacking the leader sequence and which were not of hexamer genome length. Unexpectedly, recombinant hPIV2 possessing the NP Q202A mutation could not be recovered from cDNA.
    IMPORTANCE We examined the importance of amino acids in the putative RNAbinding domain of hPIV2 NP for polymerase activity using minireplicons. Abnormally enhanced genome replication was observed upon substitution mutation of the NP Q202 position to various amino acids. Surprisingly, this mutation enabled polymerase to use minigenomes that were partially lacking the leader sequence and not of hexamer genome length. This mutation does not affect fundamental properties of NP, e.g., recognition of gene junctional and editing signals. However, the strongly enhanced polymerase activity may not be viable for the infectious life cycle. This report highlights the potential of the polymerase complex with point mutations in NP and helps our detailed understanding of the molecular basis of gene expression.

    DOI: 10.1128/JVI.02203-16

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  • Keisuke Ohta, Hideo Goto, Yusuke Matsumoto, Natsuko Yumine, Masato Tsurudome, Machiko Nishio .  Graf1 Controls the Growth of Human Parainfluenza Virus Type 2 through Inactivation of RhoA Signaling .  JOURNAL OF VIROLOGY90 ( 20 ) 9394 - 9405   2016年10月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Rho GTPases are involved in a variety of cellular activities and are regulated by guanine nucleotide exchange factors and GTPase-activating proteins (GAPs). We found that the activation of Rho GTPases by lysophosphatidic acid promotes the growth of human parainfluenza virus type 2 (hPIV-2). Furthermore, hPIV-2 infection causes activation of RhoA, a Rho GTPase. We hypothesized that Graf1 (also known as ARHGAP26), a GAP, regulates hPIV-2 growth by controlling RhoA signaling. Immunofluorescence analysis showed that hPIV-2 infection altered Graf1 localization from a homogenous distribution within the cytoplasm to granules. Graf1 colocalized with hPIV-2 P, NP, and L proteins. Graf1 interacts with P and V proteins via their N-terminal common region, and the C-terminal Src homology 3 domain-containing region of Graf1 is important for these interactions. In HEK293 cells constitutively expressing Graf1, hPIV-2 growth was inhibited, and RhoA activation was not observed during hPIV-2 infection. In contrast, Graf1 knockdown restored hPIV-2 growth and RhoA activation. Overexpression of hPIV-2 P and V proteins enhanced hPIV-2-induced RhoA activation. These results collectively suggested that hPIV-2 P and V proteins enhanced hPIV-2 growth by binding to Graf1 and that Graf1 inhibits hPIV-2 growth through RhoA inactivation.
    IMPORTANCE
    Robust growth of hPIV-2 requires Rho activation. hPIV-2 infection causes RhoA activation, which is suppressed by Graf1. Graf1 colocalizes with viral RNP (vRNP) in hPIV-2-infected cells. We found that Graf1 interacts with hPIV-2 P and V proteins. We also identified regions in these proteins which are important for this interaction. hPIV-2 P and V proteins enhanced the hPIV-2 growth via binding to Graf1, while Graf1 inhibited hPIV-2 growth through RhoA inactivation.

    DOI: 10.1128/JVI.01471-16

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  • Hideo Goto, Keisuke Ohta, Yusuke Matsumoto, Natsuko Yumine, Machiko Nishio .  Evidence that Receptor Destruction by the Sendai Virus Hemagglutinin-Neuraminidase Protein Is Responsible for Homologous Interference .  JOURNAL OF VIROLOGY90 ( 17 ) 7640 - 7646   2016年9月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Receptor destruction has been considered one of the mechanisms of homologous Sendai virus (SeV) interference. However, direct evidence of receptor destruction upon virus infection and its relevance to interference is missing. To investigate a precise mechanism of homologous interference, we established SeV persistently infected cells. The persistently infected cells inhibited superinfection by homologous SeV but supported replication of human parainfluenza virus 2 (hPIV2) and influenza A virus (IAV). We confirmed that SeV particles could not attach to or penetrate the infected cells and that the hemagglutinin-neuraminidase (HN) protein of SeV was involved in the interference. Lectin blot assays showed that the alpha 2,3-linked sialic acids were specifically reduced in the SeV-infected cells, but the level of alpha 2,6-linked sialic acids had not changed. As infection with IAV removed both alpha 2,3- and alpha 2,6-linked sialic acids, especially alpha 2,3-linked sialic acids, IAV-infected cells inhibited superinfection of SeV. These results provide concrete evidence that destruction of the specific SeV receptor, alpha 2,3-linked sialic acids, is relevant to homologous interference by SeV.
    IMPORTANCE
    Viral interference is a classically observed phenomenon, but the precise mechanism is not clear. Using SeV interference, we provide concrete evidence that reduction of the alpha 2,3-linked sialic acid receptor by the HN of SeV is closely related with viral interference. Since SeV infection resulted in decrease of only alpha 2,3-linked sialic acids, IAV, which also utilized alpha 2,6-linked sialic acids to initiate infection, superinfected the SeV-infected cells. In contrast, SeV could not superinfect the IAV-infected cells because both alpha 2,3- and alpha 2,6-linked sialic acids were removed. These results indicate that receptor destruction critically contributes to viral interference.

    DOI: 10.1128/JVI.01087-16

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  • Yusuke Matsumoto, Keisuke Ohta, Hideo Goto, Machiko Nishio .  Parainfluenza virus chimeric mini-replicons indicate a novel regulatory element in the leader promoter .  JOURNAL OF GENERAL VIROLOGY97 ( 7 ) 1520 - 1530   2016年7月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MICROBIOLOGY SOC  

    Gene expression of paramyxoviruses is regulated by genome-encoded cis-acting elements; however, whether all the required elements for viral growth have been identified is not clear. Using a mini-replicon system, it has been shown that human parainfluenza virus type 2 (hPIV2) polymerase can recognize the promoter elements of parainfluenza virus type 5 (PIV5), but reporter activity is lower in this case. We constructed a series of luciferase-encoding chimeric PIV2/5 mini-genomes that are basically hPIV2, but whose leader (le), mRNA start signal and trailer sequence are partially replaced with those of PIV5. Studies of the chimeric PIV2/5 mini-replicons demonstrated that replacement of hPIV2 le with PIV5 le results in remarkably weak luciferase expression. Further mutagenesis identified the responsible region as positions 25-30 of the PIV5 le. Using recombinant hPIV2, the impact of this region on viral life cycles was assessed. Insertion of the mutation at this region facilitated viral growth, genomic replication and mRNA transcription at the early stage of infection, which elicited severe cell damage. In contrast, at the late infection stage it caused a reduction in viral transcription. Here, we identify a novel cis-acting element in the internal region of an le sequence that is involved in the regulation of polymerase, and which contributes to maintaining a balance between viral growth and cytotoxicity.

    DOI: 10.1099/jgv.0.000479

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  • Tomoyuki Honda, Yusuke Yamamoto, Takuji Daito, Yusuke Matsumoto, Akiko Makino, Keizo Tomonaga .  Long-term expression of miRNA for RNA interference using a novel vector system based on a negative-strand RNA virus .  SCIENTIFIC REPORTS6   26154   2016年5月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    RNA interference (RNAi) has emerged as a promising technique for gene therapy. However, the safe and long-term expression of small RNA molecules is a major concern for the application of RNAi therapies in vivo. Borna disease virus (BDV), a non-segmented, negative-strand RNA virus, establishes a persistent infection without obvious cytopathic effects. Unique among animal non-retroviral RNA viruses, BDV persistently establishes a long-lasting persistent infection in the nucleus. These features make BDV ideal for RNA virus vector persistently expressing small RNAs. Here, we demonstrated that the recombinant BDV (rBDV) containing the miR-155 precursor, rBDV-miR-155, persistently expressed miR-155 and efficiently silenced its target gene. The stem region of the miR-155 precursor in rBDV-miR-155 was replaceable by any miRNA sequences of interest and that such rBDVs efficiently silence the expression of target genes. Collectively, BDV vector would be a novel RNA virus vector enabling the long-term expression of miRNAs for RNAi therapies.

    DOI: 10.1038/srep26154

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  • Yusuke Matsumoto, Keisuke Ohta, Natsuko Yumine, Hideo Goto, Machiko Nishio .  Identification of two essential aspartates for polymerase activity in parainfluenza virus L protein by a minireplicon system expressing secretory luciferase .  MICROBIOLOGY AND IMMUNOLOGY59 ( 11 ) 676 - 683   2015年11月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Gene expression of nonsegmented negative-strand RNA viruses (nsNSVs) such as parainfluenza viruses requires the RNA synthesis activity of their polymerase L protein; however, the detailed mechanism of this process is poorly understood. In this study, a parainfluenza minireplicon assay expressing secretory Gaussia luciferase (Gluc) was established to analyze large protein (L) activity. Measurement of Gluc expression in the culture medium of cells transfected with the minigenome and viral polymerase components enabled quick and concise calculation of L activity. By comparing the amino acid sequences in conserved region III (CRIII), a putative polymerase-active domain of the L protein, two strictly conserved aspartates were identified in all families of nsNSV. A series of L mutants from human parainfluenza virus type 2 and parainfluenza virus type 5 showed that these aspartates are necessary for reporter gene expression. It was also confirmed that these aspartates are important for the production of viral mRNA and antigenome cRNA, but not for a polymerase-complex formation. These findings suggest that these two aspartates are key players in the nucleotidyl transfer reaction using two metal ions.

    DOI: 10.1111/1348-0421.12329

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  • Shohei Kojima, Tomoyuki Honda, Yusuke Matsumoto, Keizo Tomonaga .  Heat stress is a potent stimulus for enhancing rescue efficiency of recombinant Borna disease virus .  MICROBIOLOGY AND IMMUNOLOGY58 ( 11 ) 636 - 642   2014年11月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Recently developed vector systems based on Borna disease virus (BDV) hold promise as platforms for efficient and stable gene delivery to the central nervous system (CNS). However, because it currently takes several weeks to rescue recombinant BDV (rBDV), an improved rescue procedure would enhance the utility of this system. Heat stress reportedly enhances the rescue efficiency of other recombinant viruses. Here, heat stress was demonstrated to increase the amount of BDV genome in persistently BDV-infected cells without obvious cytotoxicity. Further analyses suggested that the effect of heat stress on BDV infection is not caused by an increase in the activity of BDV polymerase. More cells in which BDV replication occurs were obtained in the initial phase of rBDV rescue by using heat stress than when it was not used. Thus, heat stress is a useful improvement on the published rescue procedure for rBDV. The present findings may accelerate the practical use of BDV vector systems in basic science and the clinic and thus enable broader adoption of this viral vector, which is uniquely suited for gene delivery to the CNS.

    DOI: 10.1111/1348-0421.12193

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  • Kan Fujino, Masayuki Horie, Tomoyuki Honda, Shoko Nakamura, Yusuke Matsumoto, Ivo M. B. Francischetti, Keizo Tomonaga .  Evolutionarily Conserved Interaction between the Phosphoproteins and X Proteins of Bornaviruses from Different Vertebrate Species .  PLOS ONE7 ( 12 ) e51161   2012年12月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Bornavirus, a non-segmented, negative-strand RNA viruses, is currently classified into several genetically distinct genotypes, such as Borna disease virus (BDV) and avian bornaviruses (ABVs). Recent studies revealed that bornavirus genotypes show unique sequence variability in the putative 5' untranslated region (5' UTR) of X/P mRNA, a bicistronic mRNA for the X protein and phosphoprotein (P). In this study, to understand the evolutionary relationship among the bornavirus genotypes, we investigated the functional interaction between the X and P proteins of four bornavirus genotypes, BDV, ABV genotype 4 and 5 and reptile bornavirus (RBV), the putative 5' UTRs of which exhibit variation in the length. Immunofluorescence and immunoprecipitation analyses using mammalian and avian cell lines revealed that the X proteins of bornaviruses conserve the ability to facilitate the export of P from the nucleus to the cytoplasm via interaction with P. Furthermore, we showed that inter-genotypic interactions may occur between X and P among the genotypes, except for X of RBV. In addition, a BDV minireplicon assay demonstrated that the X and P proteins of ABVs, but not RBV, can affect the polymerase activity of BDV. This study demonstrates that bornaviruses may have conserved the fundamental function of a regulatory protein during their evolution, whereas RBV has evolved distinctly from the other bornavirus genotypes.

    DOI: 10.1371/journal.pone.0051161

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  • Shoko Nakamura, Masayuki Horie, Kan Fujino, Yusuke Matsumoto, Tomoyuki Honda, Keizo Tomonaga .  Generation of Human Bronchial Epithelial Cell Lines Expressing Inactive Mutants of GALNT3 .  JOURNAL OF VETERINARY MEDICAL SCIENCE74 ( 11 ) 1493 - 1496   2012年11月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC VET SCI  

    As a tool to understand the role of mucins in the infection of respiratory viruses, we established cell lines stably expressing inactive mutants of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), which initiates O-glycosylation of mucins. We introduced single amino acid mutation into the regions essential for the enzyme activity of GALNT3 using the expression plasmid of human GALNT3 and transfected the mutant constructs into a human bronchial epithelial cell line, BEAS-2B. We showed that although the mutants of GALNT3 exhibit an authentic localization at the Golgi apparatus, the glycosylation pattern of the expressing cell lines appeared to be different from that of the cells expressing wild-type GALNT3. These results suggested that the established cell lines express inactive forms of GALNT3 and might be useful in investigation of the significance of O-glycosylation of mucins in respiratory virus infections.

    DOI: 10.1292/jvms.12-0199

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  • Yusuke Matsumoto, Yohei Hayashi, Hiroko Omori, Tomoyuki Honda, Takuji Daito, Masayuki Horie, Kazuyoshi Ikuta, Kan Fujino, Shoko Nakamura, Urs Schneider, Geoffrey Chase, Tamotsu Yoshimori, Martin Schwemmle, Keizo Tomonaga .  Bornavirus Closely Associates and Segregates with Host Chromosomes to Ensure Persistent Intranuclear Infection .  CELL HOST & MICROBE11 ( 5 ) 492 - 503   2012年5月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Bornaviruses are nonsegmented negative-strand RNA viruses that establish a persistent infection in the nucleus and occasionally integrate a DNA genome copy into the host chromosomal DNA. However, how these viruses achieve intranuclear infection remains unclear. We show that Borna disease virus (BDV), a mammalian bornavirus, closely associates with the cellular chromosome to ensure intranuclear infection. BDV generates viral factories within the nucleus using host chromatin as a scaffold. In addition, the viral ribonucleoprotein (RNP) interacts directly with the host chromosome throughout the cell cycle, using core histones as a docking platform. HMGB1, a host chromatin-remodeling DNA architectural protein, is required to stabilize RNP on chromosomes and for efficient BDV RNA transcription in the nucleus. During metaphase, the association of RNP with mitotic chromosomes allows the viral RNA to segregate into daughter cells and ensure persistent infection. Thus, bornaviruses likely evolved a chromosome-dependent life cycle to achieve stable intranuclear infection.

    DOI: 10.1016/j.chom.2012.04.009

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  • Takuji Daito, Kan Fujino, Tomoyuki Honda, Yusuke Matsumoto, Yohei Watanabe, Keizo Tomonaga .  A Novel Borna Disease Virus Vector System That Stably Expresses Foreign Proteins from an Intercistronic Noncoding Region .  JOURNAL OF VIROLOGY85 ( 23 ) 12170 - 12178   2011年12月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Borna disease virus (BDV), a nonsegmented, negative- strand RNA virus, infects a wide variety of mammalian species and readily establishes a long- lasting, persistent infection in brain cells. Therefore, this virus could be a promising candidate as a novel RNA virus vector enabling stable gene expression in the central nervous system (CNS). Previous studies demonstrated that the 5' untranslated region of the genome is the only site for insertion and expression of a foreign gene. In this study, we established a novel BDV vector in which an additional transcription cassette has been inserted into an intercistronic noncoding region between the viral phosphoprotein (P) and matrix (M) genes. The recombinant BDV (rBDV) carrying green fluorescent protein (GFP) between the P and M genes, rBDV P/ M- GFP, expressed GFP efficiently in cultured cells and rodent brains for a long period of time without attenuation. Furthermore, we generated a nonpropagating rBDV, Delta GLLP/M, which lacks the envelope glycoprotein (G) and a splicing intron within the polymerase gene (L), by the transcomplementation system with either transient or stable expression of the G gene. Interestingly, rBDV Delta GLLP/M established a persistent infection in cultured cells with stable expression of GFP in the absence of the expression of G. Using persistently infected rBDV Delta GLLP/M-infected cells, we determined the amino acid region in the cytoplasmic tail (CT) of BDV G important for the release of infectious rBDV particles and also demonstrated that the CT region may be critical for the generation of pseudotyped rBDV having vesicular stomatitis virus G protein. Our results revealed that the newly established BDV vector constitutes an alternative tool not only for stable expression of foreign genes in the CNS but also for understanding the mechanism of the release of enveloped virions.

    DOI: 10.1128/JVI.05554-11

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  • Tomoyuki Honda, Kan Fujino, Daisuke Okuzaki, Naohiro Ohtaki, Yusuke Matsumoto, Masayuki Horie, Takuji Daito, Masayuki Itoh, Keizo Tomonaga .  Upregulation of Insulin-Like Growth Factor Binding Protein 3 in Astrocytes of Transgenic Mice That Express Borna Disease Virus Phosphoprotein .  JOURNAL OF VIROLOGY85 ( 9 ) 4567 - 4571   2011年5月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    In a previous study, we demonstrated that transgenic mice that express Borna disease virus (BDV) phosphoprotein (P) in astrocytes show striking neurobehavioral abnormalities resembling those in BDV-infected animals. To understand the molecular disturbances induced by the expression of P in astrocytes, we performed microarray analysis with cultured astroglial cells transiently expressing P. We showed that expression of insulin-like growth factor binding protein 3 mRNA increases not only in P-expressing cultured cells but also in astrocytes from the cerebella of P transgenic mice (P-Tg). Furthermore, we demonstrated that insulin-like growth factor signaling is disturbed in the P-Tg cerebellum, a factor that might be involved in the increased vulnerability of Purkinje cell neurons in the brain.

    DOI: 10.1128/JVI.01817-10

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  • 松本祐介, 藤野寛, 朝長啓造 .  ボルナウイルスの基本性状 .  臨床獣医.29:12-16. 2011   2011年査読

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    記述言語:日本語  

  • Yusuke Matsumoto, Tomoyuki Miura, Hirofumi Akari, Yoshitaka Goto, Takeshi Haga .  Peripheral Blood CD4 and CD8 Double-Positive T Cells of Rhesus Macaques Become Vulnerable to Simian Immunodeficiency Virus by In Vitro Stimulation Due to the Induction of CCR5 .  JOURNAL OF VETERINARY MEDICAL SCIENCE72 ( 8 ) 1057 - 1061   2010年8月査読

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC VET SCI  

    In vivo Simian Immunodeficiency Virus (SIV) challenge of macaques demonstrated the earlier disappearance of CD4 and CD8 double-positive (DP) T cells than CD4 single-positive T cells, although its mechanism remains unclear. Here we found that peripheral DP T cells were readily induced to express CCR5, a secondary receptor for SIV, by in vitro stimulation with either concanavalin A or anti-CD3/CD28 monoclonal antibodies. Activated DP T cells were more vulnerable to SIV infection, indicating that the ability of DP T cells to readily express CCR5 after activation may hasten DP T cell death by SIV infection in vivo.

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▼全件表示

MISC

  • A novel RNA virus vector system for small RNA deliery based on Borna disease virus

    T. Honda, Y. Yamamoto, Y. Matsumoto, A. Makino, K. Tomonaga

    HUMAN GENE THERAPY   26 ( 10 )   A102 - A102   2015年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:MARY ANN LIEBERT, INC  

    Web of Science

  • 内在性ボルナウイルスEBLN の発現によるボルナ病ウイルスの感染阻害 査読

    藤野 寛, 堀江真行, 本田知之, 大東卓史, 松本祐介, 朝長啓造

    第153 回日本獣医学会学術集会. 埼玉2012 年3月27-29日   153rd   2012年

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    記述言語:日本語  

    J-GLOBAL

  • Intranuclear persistence of Borna disease virus shows a novel life cycle of RNA virus using host chromosome. 査読

    Matsumoto Y, Fujino K, Horie M, Nakamura S, Honda T, Schwemmle M, Tomonaga K

    The 10th International Student Seminar. Kyoto, 5-8 March 2012   2012年

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    記述言語:英語  

  • Characterization of Borna disease virus-induced RNA speckles in the nucleus. 査読

    Honda T, Matsumoto Y, Makino A, Fujino K, Sofiiku K, Nakamura S, Tomonaga K

    The 11th Awaji International Forum on Infection and Immunity. 11-14 September 2012   2012年

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    記述言語:英語  

  • ボルナウイルス 感染細胞における核内ウイルスRNP の制御機構の解明 査読

    本田知之, 松本祐介, 牧野晶子, 藤野 寛, 惣福 梢, 中村祥子, 朝長啓造

    第35回日本分子生物学会年会. 福岡 2012 年12月11-14日   35th   2012年

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    記述言語:日本語  

    J-GLOBAL

  • ボルナ病ウイル ス核内構造物の存在意義の解明 査読

    本田知之, 松本祐介, 牧野晶子, 藤野 寛, 惣福 梢, 中村祥子, 朝長啓造

    第60回日本ウイルス学会学術集会. 大阪 2012 年 11月13-15日   60th   2012年

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    記述言語:日本語  

    J-GLOBAL

  • Chromatin-dependent transcriptional regulation of Borna disease virus. 査読

    Matsumoto Y, Horie M, Daito T, Fujino K, Omori H, Tomonaga K

    The 18th East-Asia Joint Symposium on Biomedical Research. Shanghai China. 7-9 December 2011.   2011年

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    記述言語:英語  

  • 鳥ボルナウイルス感染状況の調査

    堀江真行, 大東卓史, 藤野寛, 松本祐介, 朝長啓造

    日本獣医学会学術集会講演要旨集   150th   2010年

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  • わが国における鳥ボルナウイルスの持続感染

    堀江真行, 上田謙吾, 上田亜希子, 大東卓史, 藤野寛, 松本祐介, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   58th   2010年

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  • ボルナウイルスを用いた新規RNAウイルスベクターの開発

    大東卓史, 堀江真行, 藤野寛, 松本祐介, 本田知之, 朝長啓造

    日本RNA学会年会要旨集   12th   2010年

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  • ボルナ病ウイルスのインテグレーションに関する研究

    堀江真行, 本田知之, 大東卓史, 藤野寛, 松本祐介, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   58th   2010年

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  • ボルナ病ウイルスの核内寄生メカニズムの解明

    松本祐介, 堀江真行, 大東卓史, 藤野寛, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   58th   2010年

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  • ボルナ病ウイルス膜糖蛋白質と粒子形成機構の解析

    大東卓史, 堀江真行, 藤野寛, 松本祐介, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   58th   2010年

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  • マトリックス及びエンベロープ遺伝子欠損型ボルナウイルスベクターの構築

    藤野寛, 大東卓史, 堀江真行, 松本祐介, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   58th   2010年

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  • 膜遺伝子欠損型ボルナ病ウイルスベクターの開発

    大東卓史, 松本祐介, 藤野寛, 堀江真行, 本田知之, 朝長啓造

    日本獣医学会学術集会講演要旨集   149th   2010年

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  • 鳥ボルナウイルスXおよびP遺伝子の相互作用の解析

    藤野寛, 堀江真行, 上田謙吾, 本田知之, 大東卓史, 松本祐介, 朝長啓造

    日本獣医学会学術集会講演要旨集   148th   2009年

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  • ボルナウイルス属ウイルスのXおよびP蛋白質の相互作用の解析

    藤野寛, 堀江真行, 本田知之, 大東卓史, 松本祐介, 生田和良, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   57th   2009年

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  • ボルナ病ウイルスのクロマチン結合に関与するウイルス因子の同定

    堀江真行, 松本祐介, 本田知之, 大東卓史, 藤野寛, 生田和良, 朝長啓造

    日本ウイルス学会学術集会プログラム・抄録集   57th   2009年

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  • 毛引き症のオオハナインコにおける鳥ボルナウイルス遺伝子の検出

    堀江真行, 上田謙吾, 藤野寛, 松本祐介, 大東卓史, 朝長啓造

    日本獣医学会学術集会講演要旨集   148th   2009年

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受賞

  • 2023年度日本ウイルス学会杉浦奨励賞

    2023年9月   日本ウイルス学会   「マイナス鎖RNAウイルスのゲノム複製基盤に関する研究」

共同研究・競争的資金等の研究

  • 牛パラミクソウイルスベクターワクチン改良・開発基盤の構築

    2023年8月 - 2024年3月

    令和5年度 鹿児島大学地域活性化研究支援事業 

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    担当区分:研究代表者 

  • 全てのパラミクソウイルスに対応する弱毒ワクチン開発機構と新規ワクチンベクターへの応用

    2023年4月 - 2025年3月

    AMED  新興・再興感染症に対する革新的医薬品等開発推進研究事業 

    松本祐介, 加藤文博, 一戸猛志

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    担当区分:研究代表者 

  • エボラウイルスゲノムの塩基数はなぜ6の倍数でなければならないのか

    2023年4月 - 2025年3月

    (公財)加藤記念バイオサイエンス振興財団  加藤記念研究助成 

    松本祐介

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    担当区分:研究代表者 

  • 牛パラミクソウイルス感染症の革新的ワクチン改良技術の構築

    2023年4月 - 2024年3月

    (一財)旗影会 2023年度研究助成 

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    担当区分:研究代表者 

  • 全てのパラミクソウイルスに対応する弱毒ワクチン開発機構と新規ワクチンベクターへの応用

    2023年4月 - 2024年3月

    東京大学医科学研究所国際共同利用・共同研究拠点 2023年度共同研究 

    松本祐介, 一戸猛志

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    担当区分:研究代表者 

  • RNAウイルスのゲノム塩基数が複製におよぼす影響の解析

    2023年4月 - 2024年3月

    京都大学医生物学研究所  ウイルス・幹細胞システム医生物学共同研究拠点 共同研究 

    松本祐介, 朝長啓造

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    担当区分:研究代表者 

  • エボラウイルス複製機構におけるRule of Six存在意義の解明

    2022年10月 - 2024年3月

    長崎大学高度感染症研究センター  新興感染症制御研究拠点 共同研究 

    松本祐介, 浦田秀造, 杉田征彦, 川崎純菜

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    担当区分:研究代表者 

  • 新型コロナウイルス感染予防ワクチン作用機序の解明

    2021年4月 - 2022年3月

    公益財団法人東京生化学研究会  2020年度研究奨励金(I) 

    松本祐介

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    担当区分:研究代表者 

  • モデルウイルスを用いたクリミア・コンゴ出血熱ウイルスの病原性解析

    2020年10月 - 2021年9月

    武田科学振興財団  医学系研究継続助成 

    松本祐介

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    担当区分:研究代表者 

  • パラミクソウイルスゲノムの塩基数はなぜ6の倍数でなければならないのか

    研究課題/領域番号:20K16266  2020年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    松本 祐介

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    パラミクソウイルスのゲノムは塩基数が6の倍数でなければ複製されないという法則によって制御されており、これはRule of sixと呼ばれている。パラミクソウイルス科に属するすべてのウイルス種はこの法則に従うが、その生物学的存在意義は長年不明であった。これまでに我々は、パラミクソウイルスの一種で、小児の呼吸器感染症の原因となるヒトパラインフルエンザウイルス2型(hPIV2)を題材とし、ウイルスのゲノム複製を数値化できるミニレプリコン系、リコンビナントウイルスを作製できるリバースジェネティクス系を駆使してこのメカニズムの解明に当たってきた。hPIV2のミニレプリコン系を用いた解析により、ゲノム複製に重要なウイルス因子である核酸(NP)蛋白の1アミノ酸変異によって、Rule of Sixを無視した複製活性を示すことを明らかにした。さらに、Rule of Sixを無視できる状態で複製可能なリコンビナントhPIV2を作製し、その感染細胞内ライフサイクルを解析した。その結果、変異ウイルスは複製時にウイルスゲノム上に余分なヌクレオチドが挿入されるエラーが高頻度に起こることがわかり、Rule of SixはRNA複製時のエラーを防ぐために存在すること、それはNP蛋白の1アミノ酸によって制御されうることを示した。本研究により、ウイルスのゲノム複製を厳密に制御するウイルス蛋白の機能の一端が明らかになり、この部位を標的とした新たな抗ウイルス薬やワクチンの開発につながることが期待できる。

  • モデルウイルスを用いたクリミア・コンゴ出血熱ウイルスの病原性解析

    2018年4月 - 2019年3月

    武田科学振興財団  医学系研究助成 

    松本 祐介

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    担当区分:研究代表者  資金種別:競争的資金

  • クリミア・コンゴ出血熱ウイルスモデル・ハザラウイルスを使用した増殖機構の解明

    研究課題/領域番号:20K07528  2017年4月 - 2020年3月

    日本学術振興会: 科学研究費助成事業  基盤研究(C)  基盤研究(C)

    西尾 真智子, 太田圭介, 松本祐介

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    担当区分:研究代表者  資金種別:競争的資金

    クリミア・コンゴ出血熱ウイルス(CCHFV)は致死性の高い人獣共通感染症の1つで、研究にはBSL4の施設が必要であり、研究をすることが難しい。そこでヒトに病気を起こさずBSL2の研究室で扱える極めて近縁のハザラウイルス(HAZV)をCCHFVの研究を進めるためのモデルウイルスに選んだ。HAZVをSW13細胞(ヒト由来)に感染させると、速やかにアポトーシスを伴う激しい細胞傷害性を示すが、細胞によって示す細胞傷害性に違いがあることが明らかになった。また、激しい細胞傷害性を示すにも関わらず感染細胞のごく一部は生き残り、幾つかの細胞で持続感染細胞株を樹立することができた。
    樹立した持続感染細胞株の中の1つは、継代を続けると細胞培養上清中よりウイルスが検出されなくなった。しかし、細胞株のcell lysateからウエスタンブロット法によりHAZVのN蛋白を検出すると、一過性感染と変わらずN蛋白が検出できた。したがって、この細胞株では、ウイルスの持続感染は継続しているが、細胞上清にウイルスが出芽できない変異が起こっていると考えられる。大変興味深い変異が入ったと考え、まずこの持続感染細胞株の解析に絞って研究を行う事にした。上清にウイルスが検出されなくなった細胞株の細胞抽出液よりウイルスの全ゲノムを検出し、塩基配列を決定した。幾つかの変異が見つかった中で、最もアミノ酸変異が多かったのはL蛋白であり、5カ所のアミノ酸変異が見つかった。これらの変異がポリメラーゼ活性に与える影響をミニゲノムの系を使って検討した。変異により活性が下がると予想したが、逆にこの変異によりポリメラーゼ活性は約10倍上昇していることが明らかになった。ここまでの研究実績をまとめ、現在論文を作成しているところである。

  • パラミクソウイルスのリーダー配列と細胞障害性の関係を探る

    研究課題/領域番号:16K19143  2016年4月 - 2019年3月

    日本学術振興会: 科学研究費助成事業  若手研究(B)  若手研究(B)

    松本 祐介

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    担当区分:研究代表者  資金種別:競争的資金

    ヒトパラインフルエンザウイルス2型の増殖機構解明のため、転写・複製機構に着目して研究を行った。ミニゲノム系・リバースジェネティクス系を用いた解析により、ウイルスゲノムのリーダー配列にわずかな変異が入ることで、転写バランスが乱れることがわかった。この変異による過剰な転写産物の蓄積によって細胞傷害性に影響を与えることがわかった。さらに、ゲノムに結合する核酸(NP)蛋白の側にも着目した研究を行った。NP蛋白のRNA結合領域の1アミノ酸に変異を加えると、ポリメラーゼがプロモーター配列を無視した複製能を持つことを見出した。このことから、NP蛋白の1アミノ酸によるゲノム複製制御機構が明らかになった。

  • 感染初期に注目したセンダイウイルス持続感染細胞における重感染阻止機構の解明

    研究課題/領域番号:15K08500  2015年4月 - 2016年3月

    日本学術振興会: 科学研究費助成事業  基盤研究(C)  基盤研究(C)

    五藤 秀男, 太田圭介, 松本祐介

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    担当区分:研究代表者  資金種別:競争的資金

    ウイルス感染の新たな制御方法の開発を目指し、「ウイルスの干渉」現象の機構を調べた。センダイウイルスでは、細胞への吸着・侵入段階で重感染が抑制された。ウイルス感染の抑制は受容体破壊因子であるウイルス蛋白質の発現と相関して認められ、細胞表面のシアル酸も感染により減少した。受容体破壊因子を持たない狂犬病ウイルスの干渉現象も、センダイウイルスと同様に細胞への吸着・侵入段階での抑制が関与した。
    以上の結果から、ウイルスの受容体破壊因子の有無に関係無く、受容体破壊がウイルスの干渉現象の主要な要因となることが明らかとなった。

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