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Dissect the role of hepatitis C virus NS2 protein in virus assembly

Research Project

Project/Area Number 21590519
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

SUZUKI Ryosuke  国立感染症研究所, ウイルス第二部, 主任研究官 (50342902)

Co-Investigator(Kenkyū-buntansha) SUZUKI Tetsuro  浜松医科大学, 医学部, 教授 (00250184)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsHCV / NS2 / 粒子形成 / 感染性粒子 / 宿主因子 / 感染性
Research Abstract

Hepatitis C virus(HCV) nonstructural protein 2(NS2) is a membrane-associated cysteine autoprotease that mediates cleavage of its own carboxyl terminus from NS3.In addition to its role in polyprotein processing, emerging evidence indicates that NS2plays crucial role in assembly of infectious virus particle. However, biological significance of NS2in the HCV assembly remains unclear. In this study, we screened human liver cDNA libraries by split-ubiquitin membrane yeast two-hybrid assay using NS2as a bait, and identified several NS2-interacting proteins. Following siRNA screening identified a membrane-associated cellular protein that is involved in HCV production. Gene silencing of the host factor resulted in no effect on the entry and RNA replication of HCV, suggesting that this host factor is involved in HCV assembly step. Interaction of the host factor with NS2 in mammalian cells was confirmed. Finding of this study may provide important information for understanding the molecular mechanism of assembly and formation of infectious HCV particles.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (47 results)

All 2012 2011 2010 2009 Other

All Journal Article (11 results) (of which Peer Reviewed: 7 results) Presentation (34 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Visualization and Measurement of ATP Levels in Living Cells Replicating Hepatitis C Virus Genome RNA2012

    • Author(s)
      安東友美
    • Journal Title

      PLoS Pathogens

      Volume: 8 Issue: 3 Pages: e1002561-e1002561

    • DOI

      10.1371/journal.ppat.1002561

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of the endoplasmic reticulum-associated degradation(ERAD) pathway in degradation of hepatitis C virus envelope proteins and production of virus particles2011

    • Author(s)
      SaeedM, Suzuki R, Watanabe N, Masaki T, Tomonaga M, Muhammad A, Kato T, Matsuura Y, Watanabe H, Wakita T, Suzuki T
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 37264-73

    • Related Report
      2011 Final Research Report
  • [Journal Article] Analyses of mutations selected by passaging a chimeric flavivirus identify mutations that alter infectivity and reveal an interaction between the structural proteins and the nonstructural glycoprotein NS12011

    • Author(s)
      Winkelmann ER, Widman DG, Suzuki R, Mason PW
    • Journal Title

      Virology

      Volume: 421(2) Pages: 96-104

    • Related Report
      2011 Final Research Report
  • [Journal Article] Analyses of mutations selected by passaging a chimeric flavivirus identify mutations that alter infectivity and reveal an interaction be tween the structural proteins and the nonstructural glycoprotein NS12011

    • Author(s)
      Winkelmann ER, Widman DG, Suzuk R, Mason PW
    • Journal Title

      Virology

      Volume: 421 Pages: 96-104

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of the ERAD pathway in degradation of hepatitis C virus envelope proteins and production of virus particles2011

    • Author(s)
      Saeed M, Suzuki R, Watanabe N, Masaki T, Tomonaga M, Muhammad A, Kato T, Matsuura Y, Watanabe H, Wakita T, Suzuki T
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Pages: 37264-37273

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of infectious hepatitis C virus by using RNA polymerase I-mediated transcription2010

    • Author(s)
      Masaki T, Suzuki R, Saeed M, Mori K, Matsuda M, Aizaki H, Ishii K, Maki N, Miyamura T, Matsuura Y, Wakita T, Suzuki T
    • Journal Title

      J Virol

      Volume: 84 Issue: 11 Pages: 5824-35

    • DOI

      10.1128/jvi.02397-09

    • Related Report
      2011 Final Research Report
  • [Journal Article] Involvement of PA28g in the propagation of hepatitis C virus2010

    • Author(s)
      Moriishi K., Shoji I., Mori Y., Suzuki R., Suzuki T., Kataoka C., and Matsuura Y.
    • Journal Title

      Hepatology

      Volume: 52 Issue: 2 Pages: 411-420

    • DOI

      10.1002/hep.23680

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Production of infectious hepatitis C virus by using RNA polymerase I-mediated transcription2010

    • Author(s)
      Masaki T, Suzuki R, Saeed M, Mori K, Matsuda M, Aizaki H, Ishii K, Maki N, Miyamura T, Matsuura Y, Wakita T, Suzuki T
    • Journal Title

      J.Virol. 84

      Pages: 5824-5835

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of hepatitis C virus core antigen assays in detecting recombinant viral antigens of various genotypes2009

    • Author(s)
      Saeed M, Suzuki R, Kondo M, Aizaki H, Kato T, Mizuochi T, Wakita T, Watanabe H, Suzuki T
    • Journal Title

      J Clin Microbiol

      Volume: 47 Issue: 12 Pages: 4141-3

    • DOI

      10.1128/jcm.01437-09

    • Related Report
      2011 Final Research Report
  • [Journal Article] Evaluation of hepatitis C virus core antigen assays for detecting recombinant viral antigens derived from various genotypes2009

    • Author(s)
      Saeed M, Suzuki R, Kondo M, Aizaki H, Kato T, Mizuochi T, Wakita T, Suzuki T.
    • Journal Title

      J Clin.Micro. 47

      Pages: 4141-4143

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of PA28g in the propagation of hepatitis C virus

    • Author(s)
      Moriishi K, Shoji I, Mori Y, Suzuki R, Suzuki T, Kataoka C, Matsuura Y.
    • Journal Title

      Hepatology (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Identification of lipid droplet? associated membrane proteins that are involved in HCV production2011

    • Author(s)
      Aizaki H, Matsumoto Y, Goto K, Watashi K, Suzuki R, Fukasawa M, Hanada K, Sato S, Takahashi N, Matsuura Y, Motojima K, Miyamura T, Suzuki T, WakitaT
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification and functional analysis of small molecules inhibiting the late step of hepatitis C virus life cycle2011

    • Author(s)
      Watashi K, Uchida N, Suzuki R, Aizaki H, Wakita T
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Small molecules that elicit strong anti? HCV activity through down? modulation of HCV entry receptor2011

    • Author(s)
      Takebe Y, Uenishi R, Tani H, Suzuki R, Takagi M, Hase S, Liao H, Tsuchiura T, Shinya K, Wakita T, Matsuura Y, Patel A
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Isolation of a highly infectious hepatitis C virus with adaptive mutations2011

    • Author(s)
      Fukasawa M, Shirasago Y, Saito K, Murakami Y, Fukasawa H, Suzuki T, Suzuki R, Wakita T, Hanada K, Chiba J
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of novel NS5A? associated proteins in the host? cell membrane fraction and their role in HCV life cycle2011

    • Author(s)
      Goto K, Kimura T, Watashi K, Suzuki R, Yamagoe S, Miyamura T, Moriya K, Yotsuyanagi H, Koike K, Suzuki T, Wakita T, Aizaki H
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Halopemide inhibited a post? assembly step in hepatitis C virus life cycle2011

    • Author(s)
      Uchida N, Watashi K, Suzuki R, Aizaki H, Chiba J, Wakita T
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Signal peptidase complex 1 participates in the assembly of hepatitis C virus through an interaction with NS22011

    • Author(s)
      Suzuki R, Suzuki T, Saito K, Matsuda M, Watashi K, Matsuura Y, Wakita T, Aizaki H
    • Organizer
      18th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of host factor that interacts with hepatitis C virus NS2protein and is involved in the viral assembly2011

    • Author(s)
      Suzuki R, Suzuki T, Saito K, Matsuda M, Watashi K, Matsuura Y, Wakita K, Aizaki H
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of small molecules affecting late steps of hepatitis C virus life cycle2011

    • Author(s)
      Watashi K, Uchida N, Suzuki R, Aizaki H, Wakita T
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Antiviral activity of glycyrrhizin against hepatitis C virus in vitro2011

    • Author(s)
      Matsumoto Y, Watashi K, Suzuki R, Matsuura Y, Suzuki T, Miyamura T, Wake K, Wakita T, Aizaki H
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of lipid droplet-associated membrane proteins that are involved in HCV production2011

    • Author(s)
      Aizaki H, Matsumoto Y, Goto K, Watashi K, Suzuki R, Fukasawa M, Hanada K, Sato S, Takahashi N, Matsuura Y, Motojima K, Miyamura T, Suzuki T, Wakita T
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification and functional analysis of small molecules in hibiting the late step of hepatitis C virus life cycle2011

    • Author(s)
      Watashi K, Uchida N, Suzuki R, Aizaki H, Wakita T
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Small molecules that elicit strong anti-HCV activity through down-modulation of HCV entry receptor2011

    • Author(s)
      Takebe Y, Uenishi R, Tani H, Suzuki R, Takagi M, Hase S, Liao H, Tsuchiura T, Shinya K, Wakita T, Matsuura Y, Patel A
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Isolation of a highly infectious hepatitis C virus with adaptive mutations2011

    • Author(s)
      Fukasawa M, Shirasago Y, Saito K, Murakami Y, Fukazawa H, Suzuki T, Suzuki R, Wakita T, Hanada K, Chiba J
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of novel NS5A-associated proteins in the host-cell membrane fraction and their role in HCV life cycle2011

    • Author(s)
      Goto K, Kimura T, Watashi K, Suzuki R, Yamagoe S, Miyamura T, Moriya K, Yotsuyanagi H, Koike K, Suzuki T, Wakita T, Aizaki H
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Halopemide inhibited a post-assembly step in hepatitis C virus life cycle2011

    • Author(s)
      Uchida N, Watashi K, Suzuki R, Aizaki H, Chiba J, Wakita T
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Signal peptidase complex 1 participates in the assembly of hepatitis C virus through an interaction with NS22011

    • Author(s)
      Suzuki R, Suzuki T, Saito K, Matsuda M, Watashi K, Matsuura Y, Wakita T, Aizaki H
    • Organizer
      第18回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、シアトル
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of host factor that interacts with hepatitis C virus NS2 protein and is involved in the viral assembly2011

    • Author(s)
      Suzuki R, Suzuki T, Saito K, Matsuda M, Watashi K, Matsuura Y, Wakita T, Aizaki H
    • Organizer
      第15回国際ウイルス学会
    • Place of Presentation
      札幌
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of small molecules affecting late steps of he patitis C virus life cycle2011

    • Author(s)
      Watashi K, Uchida N, Suzuki R, Aizaki H, Wakita T
    • Organizer
      第15回国際ウイルス学会
    • Place of Presentation
      札幌
    • Related Report
      2011 Annual Research Report
  • [Presentation] Antiviral activity of glycyrrhizin against hepatitis C virus in vitro2011

    • Author(s)
      Matsumoto Y, Watashi K, Suzuki R, Matsuura Y, Suzuki T, Miyamura T, Wake K, Wakita T, Aizaki H
    • Organizer
      第15回国際ウイルス学会
    • Place of Presentation
      札幌
    • Related Report
      2011 Annual Research Report
  • [Presentation] Entry mechanisms of hepatitis C virus examined by trans-complemented particles2010

    • Author(s)
      Suzuki R, Alazawa D, Ishii K, Matsuura Y, Wakita T, Suzuki T
    • Organizer
      9th International Symposium on Positive-Strand RNA Viruses
    • Place of Presentation
      Atlanta, GA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Efficient production of trans-complemented hepatitis C virus particles : Use for study of viral entry process2010

    • Author(s)
      Suzuki R, Alazawa D, Ishii K, Matsuura Y, Wakita T, Suzuki T
    • Organizer
      17th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] C型肝炎ウイルスのtrans-packaging型粒子を用いた感染機構の解析2010

    • Author(s)
      鈴木亮介、斎藤憲司、赤澤大輔、石井孝司、松浦善治、脇田隆字、鈴木哲朗
    • Organizer
      日本ウイルス学会第58回学術集会
    • Place of Presentation
      徳島
    • Related Report
      2011 Final Research Report
  • [Presentation] 分割ユビキチン法を利用したHCV NS2と結合する宿主因子の探索およびウイルス粒子形成への関与2010

    • Author(s)
      鈴木亮介、相崎英樹、脇田隆字、鈴木哲朗
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸市
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Entry mechanisms of hepatitis C virus examined by trans-complemented particles2010

    • Author(s)
      Ryosuke Suzuki, Daisuke Akazawa, Koji Ishii, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
    • Organizer
      第9回プラス鎖RNAウイルスに関する国際研究集会
    • Place of Presentation
      アメリカ、アトランタ
    • Related Report
      2010 Annual Research Report
  • [Presentation] Efficient production of traps-complemented hepatitis C virus particles : Use for study of viral entry process2010

    • Author(s)
      Ryosuke Suzuki, Daisuke Akazawa, Koji Ishii, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
    • Organizer
      第17回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      横浜市
    • Related Report
      2010 Annual Research Report
  • [Presentation] C型肝炎ウイルスのtrans-packaging型粒子を用いた感染機構の解析2010

    • Author(s)
      鈴木亮介、斎藤憲司、赤澤大輔、石井孝司、松浦善治、脇田隆字、鈴木哲朗
    • Organizer
      第58回日本ウイルス学会学術集会
    • Place of Presentation
      徳島市
    • Related Report
      2010 Annual Research Report
  • [Presentation] Involvement of PA28gamma and E6AP in the degradation of HCV core protein and the viral production2009

    • Author(s)
      Moriishi K, Shoji I, Suzuki R, Suzuki T, Matsuura Y
    • Organizer
      16th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Nice, France
    • Related Report
      2011 Final Research Report
  • [Presentation] Plasmid-based production of trans-complemented HCV particles : its use for functional analysis of NS22009

    • Author(s)
      Suzuki R, Saito K, Ando T, Ishii K, Matsuura Y, Miyamura T, Wakita T, Suzuki T
    • Organizer
      16th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Nice, France
    • Related Report
      2011 Final Research Report
  • [Presentation] HCVコア蛋白質のプロテアソームによる分解とウイルス産生制御2009

    • Author(s)
      森石恒司、勝二郁夫、鈴木亮介、鈴木哲朗、松浦善治
    • Organizer
      日本ウイルス学会第57回学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] C型肝炎ウイルスのtrans-packaging系を用いたNS2蛋白質の感染性粒子形成における機能解析2009

    • Author(s)
      鈴木亮介、斎藤憲司、安東友美、石井孝司、松浦善治、宮村達男、脇田隆字、鈴木哲朗
    • Organizer
      日本ウイルス学会第57回学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Prohibitin2はC型肝炎ウイルス(HCV) NS5A蛋白と相互作用しHCV複製調節に働く2009

    • Author(s)
      木村敬郎、鈴木亮介、山越智、鈴木健裕、堂前直、勝二郁夫、松浦善治、千葉丈、脇田隆字、鈴木哲朗
    • Organizer
      日本ウイルス学会第57回学術集会
    • Related Report
      2011 Final Research Report
  • [Presentation] Plasmid-based production of trans-complemented HCV particles : its use for functional analysis of NS22009

    • Author(s)
      鈴木亮介, 斎藤憲司, 安東友美, 石井孝司, 松浦善治, 宮村達男, 脇田隆字, 鈴木哲朗
    • Organizer
      第16回C型肝炎ウイルス及び関連ウイルスに関する国際研究集会
    • Place of Presentation
      フランス、ニース
    • Related Report
      2009 Annual Research Report
  • [Presentation] C型肝炎ウイルスNS2蛋白質が感染性粒子形成に関与するメカニズムの解明2009

    • Author(s)
      鈴木亮介、斎藤憲司、安東友美、石井孝司、松浦善治、宮村達男、脇田隆字、鈴木哲朗
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] C型肝炎ウイルス粒子高生産系

    • Inventor(s)
      脇田隆字、石井孝司、鈴木哲朗、鈴木亮介、宮村達男、田邉純一、曽根三郎
    • Related Report
      2011 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 新規組換え型ヒトC型肝炎ウイルス様粒子とその産生方法

    • Inventor(s)
      脇田隆字、石井孝司、鈴木哲朗、鈴木亮介、宮村達男、田邉純一、曽根三郎
    • Related Report
      2011 Final Research Report
    • Overseas

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Published: 2009-04-01   Modified: 2016-04-21  

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