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molecular basis of immune evasion by RNA virus

Research Project

Project/Area Number 17K07296
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionHokkaido University

Principal Investigator

Ose Toyoyuki  北海道大学, 先端生命科学研究院, 准教授 (80380525)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsRNAウイルス / 結晶構造解析 / 分子間相互作用 / 相互作用解析 / 組換え調製 / 免疫不活化 / 転写
Outline of Final Research Achievements

To evade host immunity, many pathogenic viruses inactivate host JAK-STAT pathways using diverse strategies. Measles virus utilizes P and V proteins to counteract this signaling pathway. Our data indicate that interactions between the C-terminal domain (CTD) of V and STAT2 is one order of magnitude stronger than that of the N-terminal region of V and STAT1. We also clarified those interactions are completely independent each other in solution. These results provide a novel model that MeV-V can not only inhibit the STAT2/IRF9 interaction but also disrupt pre-assembled ISGF3. For CTD of rabies virus P protein, we analyze the structures of the CTD of P of Duvenhage and of a distinct rabies virus strain to gain further insight on the nature and potential function of the hydrophobic surface. Molecular contacts suggest that the hydrophobic patch is important to intermolecular interactions with other proteins, which differ between the lyssavirus species.

Academic Significance and Societal Importance of the Research Achievements

ウイルスがどの宿主・細胞に感染できるかは,細胞表面におけるウイルス蛋白質―細胞受容体の親和性だけでは説明できない。すなわち,第2因子である,宿主免疫系をかいくぐるウイルスの巧妙な策略を解明することが重要である。ここでは,免疫シグナル経路であるJAK-STAT系を構成するSTAT分子に対して,人類に対する影響が大きい麻疹ウイルス,狂犬病ウイルスが免疫系逃避のために使用している蛋白質の相互作用解析を通して,その指向性を明らかにした。精密な解離定数解析を通し,麻疹ウイルスV蛋白質はSTAT2とIRF9の相互作用を阻害するだけで無く,すでに結合状態にある両者の結合を剥がすことができることも判明した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (9 results)

  • [Int'l Joint Research] Monash University/University of Melbourne(オーストラリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Melbourne/Monash University(オーストラリア)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation2020

    • Author(s)
      Hirao Kengo、Andrews Sophie、Kuroki Kimiko、Kusaka Hiroki、Tadokoro Takashi、Kita Shunsuke、Ose Toyoyuki、Rowland-Jones Sarah L.、Maenaka Katsumi
    • Journal Title

      iScience

      Volume: 23 Issue: 1 Pages: 100758-100758

    • DOI

      10.1016/j.isci.2019.100758

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficient preparation of human and mouse CD1d proteins using silkworm baculovirus expression system2020

    • Author(s)
      Kusaka Hiroki、Kita Shunsuke、Tadokoro Takashi、Yoshida Kouki、Kasai Yoshiyuki、Niiyama Harumi、Fujimoto Yukari、Hanashima Shinya、Murata Michio、Sugiyama Shigeru、Ose Toyoyuki、Kuroki Kimiko、Maenaka Katsumi
    • Journal Title

      Protein Expression and Purification

      Volume: 172 Pages: 105631-105631

    • DOI

      10.1016/j.pep.2020.105631

    • NAID

      120007147244

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1H, 15N and 13C resonance assignments of the C-terminal domain of the P protein of the Nishigahara strain of rabies virus.2019

    • Author(s)
      Zhan J, Hossain MA, Sethi A, Ose T, Moseley GW, Gooley PR
    • Journal Title

      Biomolecular NMR assignments

      Volume: 13 Pages: 5-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biophysical characterization and single‐chain Fv construction of a neutralizing antibody to measles virus2019

    • Author(s)
      Tadokoro Takashi、Jahan Mst Lubna、Ito Yuri、Tahara Maino、Chen Surui、Imai Atsutoshi、Sugimura Natsumi、Yoshida Koki、Saito Mizuki、Ose Toyoyuki、Hashiguchi Takao、Takeda Makoto、Fukuhara Hideo、Maenaka Katsumi
    • Journal Title

      The FEBS Journal

      Volume: 287 Issue: 1 Pages: 145-159

    • DOI

      10.1111/febs.14991

    • NAID

      120006866527

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Specificity of Morbillivirus Hemagglutinins to Recognize SLAM of Different Species2019

    • Author(s)
      Fukuhara Hideo、Ito Yuri、Sako Miyuki、Kajikawa Mizuho、Yoshida Koki、Seki Fumio、Mwaba Mwila Hilton、Hashiguchi Takao、Higashibata Masa-aki、Ose Toyoyuki、Kuroki Kimiko、Takeda Makoto、Maenaka Katsumi
    • Journal Title

      Viruses

      Volume: 11 Issue: 8 Pages: 761-761

    • DOI

      10.3390/v11080761

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural and Functional Basis for LILRB Immune Checkpoint Receptor Recognition of HLA-G Isoforms2019

    • Author(s)
      Kuroki Kimiko、Matsubara Haruki、Kanda Ryo、Miyashita Naoyuki、Shiroishi Mitsunori、Fukunaga Yuko、Kamishikiryo Jun、Fukunaga Atsushi、Fukuhara Hideo、Hirose Kaoru、Hunt Joan S.、Sugita Yuji、Kita Shunsuke、Ose Toyoyuki、Maenaka Katsumi
    • Journal Title

      The Journal of Immunology

      Volume: 203 Issue: 12 Pages: 3386-3394

    • DOI

      10.4049/jimmunol.1900562

    • NAID

      120007018379

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface2019

    • Author(s)
      Hossain Md. Alamgir、Larrous Florence、Rawlinson Stephen M.、Zhan Jingyu、Sethi Ashish、Ibrahim Youssef、Aloi Maria、Lieu Kim G.、Mok Yee-Foong、Griffin Michael D.W.、Ito Naoto、Ose Toyoyuki、Bourhy Herv?、Moseley Gregory W.、Gooley Paul R.
    • Journal Title

      Cell Reports

      Volume: 29 Issue: 7 Pages: 1934-1945.e8

    • DOI

      10.1016/j.celrep.2019.10.020

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 1H, 15N and 13C resonance assignments of the C-terminal domain of the P protein of the Nishigahara strain of rabies virus2018

    • Author(s)
      Zhan Jingyu、Hossain Md. Alamgir、Sethi Ashish、Ose Toyoyuki、Moseley Gregory W.、Gooley Paul R.
    • Journal Title

      Biomolecular NMR Assignments

      Volume: 13 Issue: 1 Pages: 5-8

    • DOI

      10.1007/s12104-018-9841-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 狂犬病ウイルスP蛋白質によるJAK-STATシグナル阻害機構の解明2020

    • Author(s)
      杉山 葵,蒋欣欣,永野悠馬,前仲 勝実,姚閔,杉田征彦,廣瀬未果,Gregory Moseley ,尾瀬 農之
    • Organizer
      Negative Strand Virus - Japan
    • Related Report
      2019 Annual Research Report
  • [Presentation] 狂犬病ウイルスP蛋白質によるJAK-STATシグナル阻害機構の解明2019

    • Author(s)
      杉山葵,蒋欣欣,永野悠馬,野間井智,若原拓也,前仲勝実,姚閔,Gregory Mosley,尾瀬農之
    • Organizer
      蛋白質科学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] STAP-2の介在によりBreast tumor kinaseがSTATを活性化する機構の解明2019

    • Author(s)
      中迫純希,松尾友樹,神田諒,田中睦乃,姚閔,松田正,前仲勝実,尾瀬農之
    • Organizer
      日本生物物理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 狂犬病ウイルスP蛋白質によるJAK-STATシグナル阻害機構の解明2019

    • Author(s)
      杉山葵,蒋欣欣,永野悠馬,野間井智,若原拓也,前仲勝実,姚閔,Gregory Mosley, 尾瀬農之
    • Organizer
      2018年度生物物理学会北海道支部会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒトの自然免疫系を阻害する麻疹ウイルスV蛋白質の機能解析2018

    • Author(s)
      永野悠馬、若原拓也、秦玉瑩、柳雄介、前仲勝実、尾瀬農之
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 狂犬病ウイルスP蛋白質によるJAK-STATシグナル阻害機構の解明2018

    • Author(s)
      杉山葵,蒋欣欣,永野悠馬,野間井智,若原拓也,前仲勝実,姚閔,Gregory Mosley, 尾瀬農之
    • Organizer
      第18回日本蛋白質科学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒトの自然免疫系を阻害する麻疹ウイルスV蛋白質の機能解2018

    • Author(s)
      永野 悠馬、若原 拓也、秦玉瑩、柳 雄介、前仲 勝実、尾瀬 農之
    • Organizer
      日本蛋白質科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 狂犬病ウイルスP蛋白質によるJAK-STATシグナル阻害機構の解明2018

    • Author(s)
      杉山葵,蒋欣欣,永野 悠馬,野間井智,若原拓也,前仲勝実,姚閔,尾瀬農之
    • Organizer
      日本蛋白質科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Functional analysis of the rabies virus protein that inhibits IFN signaling2017

    • Author(s)
      Xinxin Jiang, Uma Nagano, Tomo Nomai, Takuya Wakahara, Katsumi Maenaka, Gregory Mosley, and Toyoyuki Ose
    • Organizer
      日本蛋白質科学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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