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Sttudy of host proteases that activate influenza viruses in vivo

Research Project

Project/Area Number 26293105
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Takeda Makoto  国立感染症研究所, ウイルス第三部, 部長 (40311401)

Co-Investigator(Renkei-kenkyūsha) SAKAI Kouji  国立感染症研究所, ウイルス第三部, 主任研究官 (70515535)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsプロテアーゼ / インフルエンザウイルス / パラミクソウイルス / センダイウイルス / 開裂 / パラインフルエンザウイルス / ウィルス / ウイルス / TMPRSS2
Outline of Final Research Achievements

Using knockout (KO) mice we have previously revealed that TMPRSS2, which is expressed on epithelia of the respiratory tract is an essential protease for proteolytic activation of influenza viruses. In TMPRSS2 KO mice the hemagglutinin (HA) of influenza viruses remained to be uncleared and virus replication was severely impaired. In the present study we focused on Sendai virus, a member of the Paramyxoviridae family, because mice are the natural host of Sendai virus and Sendai virus also requires host proteases for its activation in vivo. Sendai virus showed a lethal infection for wild type mice, while TMPRSS2 KO mice were resistant to the Sendai virus infection. The replication of Sendai virus was severely restricted in the TMPRSS2 KO mice. These data for the first time demonstrated that TMPRSS2 is the essential protease for proteolytic activation of an ARI virus, Sendai virus, in the natural host.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (8 results)

All 2016 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] A Mutant H3N2 Influenza Virus Uses an Alternative Activation Mechanism in TMPRSS2 Knockout Mice by Loss of an Oligosaccharide in the Hemagglutinin Stalk Region2015

    • Author(s)
      Sakai K, Sekizuka T, Ami Y, Nakajima N, Kitazawa M, Sato Y, Nakajima K, Anraku M, Kubota T, Komase K, Takehara K, Hasegawa H, Odagiri T, Tashiro M, Kuroda M, Takeda M
    • Journal Title

      J Virol

      Volume: 89 Issue: 9 Pages: 5154-5158

    • DOI

      10.1128/jvi.00124-15

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Host Protease TMPRSS2 Plays a Major Role in In Vivo Replication of Emerging H7N9 and Seasonal Influenza Viruses2014

    • Author(s)
      Sakai K, Ami Y, Tahara M, Kubota T, Anraku M, Abe M, Nakajima N, Sekizuka T, Shirato K, Suzaki Y, Ainai A, Nakatsu Y, Kanou K, Nakamura K, Suzuki T, Komase K, Nobusawa E, Maenaka K, Kuroda M, Hasegawa H et al
    • Journal Title

      J Virol

      Volume: 88 Issue: 10 Pages: 5608-5616

    • DOI

      10.1128/jvi.03677-13

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 呼吸病ウイルスの病原性発現に関わる宿主プロテアーゼTMPRSS2の意義2016

    • Author(s)
      酒井宏治、中島典子、駒瀬勝啓、竹田誠
    • Organizer
      第57回日本臨床ウイルス学会
    • Place of Presentation
      郡山
    • Year and Date
      2016-06-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] A natural host model revealed the essential role of the host protease TMPRSS2 for respiratory paramyxovirus pathogenicity.2015

    • Author(s)
      Takeda M, Sakai K, Ami Y, Kitazawa M, Nakajima K, Natthanan S, Anraku M, Nakajima N, Komase K, Takehara K, Hasegawa H, Tashiro M.
    • Organizer
      第63回日本ウイルス学会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Host and viral determinants of proteolytic activation of influenza viruses2015

    • Author(s)
      Sakai K, Ami Y, Kitazawa M, Nakajima K, Sekizuka T, Nakajima N, Anraku M, Tahara M, Kubota T, Komase K, Takehara K, Odagiri T, Kuroda M, Hasegawa H, Kawaoka Y, Tashiro M, Takeda M
    • Organizer
      第16回マイナス鎖RNAウイルス国際会議
    • Place of Presentation
      イタリア、シエナ市
    • Year and Date
      2015-06-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The host protease TMPRSS2 is essential for influenza A virus pathogenicity.2014

    • Author(s)
      95.Sakai K, Ami Y, Tahara M, Kubota T, Anraku M, Nakajima N, Sekizuka T, Komase K, Kuroda M, Hasegawa H, Kawaoka Y, Tashiro M, Takeda M.
    • Organizer
      The 13th Awaji International Forum on Infection and Immunity in Nara.
    • Place of Presentation
      Nara, Japan
    • Year and Date
      2014-09-23 – 2014-09-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] The host protease TMPRSS2 plays a major role for influenza virus replication in vivo.2014

    • Author(s)
      90.Sakai K, Ami Y, Tahara M, Kubota T, Nakajima N, Kuroda M, Hasegawa H, Kawaoka Y, Tashiro M, Takeda M.
    • Organizer
      16th IUMS International Congress of Virology.
    • Place of Presentation
      Montreal, Canada
    • Year and Date
      2014-07-27 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Remarks] ウイルス第三部

    • URL

      http://www.nih.go.jp/niid/ja/from-vir3.html

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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