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2010 Fiscal Year Final Research Report

Cell entry mechanisms of coronaviruses : To detect the conformational changes of viral fusion protein.

Research Project

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Project/Area Number 19790346
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

MATSUYAMA Shutoku  National Institute of Infectious Diseases, ウイルス第三部第四室, 室長 (90373399)

Project Period (FY) 2007 – 2010
KeywordsS蛋白 / エンベロープ / 構造変化中間体 / 感染 / 膜融合 / ウイルス / MHV
Research Abstract

Previous studies have demonstrated that the SARS-CoV S protein requires proteolytic cleavage by elastase, cathepsin or TMPRSS2 for S-mediated cell-cell or virus-cell membrane fusion. Activation of viral glycoprotein (GP) by protease also has been reported for influenza virus. The most distinctive difference between influenza virus and SARS-CoV is the stage during virus replication in which viral glycoproteins are cleaved by proteases. In influenza virus, the protease makes a simple cut in the GP during maturation. In contrast, SARS-CoV S protein is cleaved by the protease following receptor-induced conformational changes. The protease cleavage site in S protein is thought to be exposed only after receptor binding. In support of this model, we reported that the S protein of mouse hepatitis virus type 2 (MHV-2), which is highly similar to the S protein of SARS-CoV, requires two-step conformational changes mediated by sequential receptor binding and proteolysis to be activated for membrane fusion. Such a mechanism allows for tight temporal control over fusion by protecting the activating cleavage site from premature proteolysis yet allowing efficient cleavage upon binding to the receptor on target cells.

  • Research Products

    (16 results)

All 2011 2010 2009 2008

All Journal Article (8 results) Presentation (8 results)

  • [Journal Article] Protease dependent cell entry mechanism of Coronaviruses.2011

    • Author(s)
      Matsuyama S.
    • Journal Title

      Uirusu (review) (in press)

  • [Journal Article] Spongiform degeneration induced by neuropathogenic murine coronavirus infection.2011

    • Author(s)
      Kashiwazaki H, Nomura R, Matsuyama S, Taguchi F Watanabe R.
    • Journal Title

      Pathology international 61

      Pages: 184-191

  • [Journal Article] Characterization of a variant virus from ascitic fluid of subacute granulomatous serositis in interferon-gamma-deficient C57BL/6 mice persistently infected with murine coronavirus strain JHM.2010

    • Author(s)
      Kyuwa S, Takagaki S, Matsuyama S, Taguchi F, Saegusa J, Iwakura Y, Tagawa Y-I Yoshikawa Y.
    • Journal Title

      Viral immunology 23

      Pages: 437-442

  • [Journal Article] Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2.2010

    • Author(s)
      Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M Taguchi F.
    • Journal Title

      Journal of virology 84

      Pages: 12658-12664

  • [Journal Article] Two-step conformational changes in a coronavirus envelope glycoprotein mediated by receptor binding and proteolysis.2009

    • Author(s)
      Matsuyama S Taguchi F.
    • Journal Title

      Journal of virology 83

      Pages: 11133-11141

  • [Journal Article] Cell entry mechanisms of coronaviruses.2009

    • Author(s)
      Taguchi F Matsuyama S.
    • Journal Title

      Uirusu review 59

      Pages: 215-222

  • [Journal Article] Protease-mediated entry via the endosome of human coronavirus 229E.2008

    • Author(s)
      Kawase M, Shirato K, Matsuyama S Taguchi F.
    • Journal Title

      Journal of virology 83

      Pages: 712-721

  • [Journal Article] Entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved S protein as revealed by pseudotype virus bearing cleaved S protein.2008

    • Author(s)
      Watanabe R, Matsuyama S, Shirato K, Maejima M, Fukushi S, Morikawa S Taguchi F.
    • Journal Title

      Journal of virology 82

      Pages: 11985-11991

  • [Presentation] 宿主プロテアーゼの関与するSARSコロナウイルスの組織指向性について2010

    • Author(s)
      松山州徳
    • Organizer
      第58回日本ウイルス学会学術集会、シンポジウム9
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-09
  • [Presentation] コロナウイルス細胞侵入機構の解明2010

    • Author(s)
      松山州徳
    • Organizer
      第58回日本ウイルス学会学術集会杉浦奨励賞受賞講演
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-07
  • [Presentation] Proteolytic activation of SARS coronavirus spike protein by the transmembrane protease, TMPRSS22010

    • Author(s)
      Shutoku Matsuyama, Noriyo Nagata, Kazuya Shirato, Miyuki Kawase, Makoto Takeda, Makoto Ujike, Fumihiro Taguchi
    • Organizer
      The 10th Awaji International Forum on Infection and Immunity、ポスター
    • Place of Presentation
      淡路島
    • Year and Date
      2010-09-08
  • [Presentation] Activation of SARS-coronavirus spike protein by transmembrane protease,TMPRSS2.2010

    • Author(s)
      Shutoku Matsuyamal, Noriyo Nagatal, Makoto Takedal, Fumihiro Taguchi
    • Organizer
      The American Society for Virology 29th Annual Meeting、ポスター
    • Place of Presentation
      Montana
    • Year and Date
      2010-07-17
  • [Presentation] 膜貫通型プロテアーゼ(TMPRSS2)によるSARSコロナウイルスの細胞侵入活性化機構2010

    • Author(s)
      松山州徳、永田典代、竹田誠、氏家誠、白戸憲也、田口文広
    • Organizer
      第62回日本細胞生物学会学術集会、ポスター
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-19
  • [Presentation] Conformational Changes Mediated by Receptor Binding and Proteolysis of a Murine Coronavirus Spike protein.2009

    • Author(s)
      Matsuyama S, Taguchi F.
    • Organizer
      28th ASV Meeting
    • Place of Presentation
      The University of British Columbia, Vancouver, Canada
    • Year and Date
      20090711-20090715
  • [Presentation] コロナウイルス感染過程における膜融合について2009

    • Author(s)
      松山州徳、田口文広
    • Organizer
      第61回日本細胞生物学会大会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      20090600
  • [Presentation] マウスコロナウイルスSタンパクの2段階構造変化の解析2008

    • Author(s)
      松山州徳、田口文広
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山
    • Year and Date
      20081000

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Published: 2012-02-13   Modified: 2016-04-21  

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