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The importance of sphingolipids in Hepatitis C virus replication

Research Project

Project/Area Number 20790715
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Infectious disease medicine
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

HIRATA Yuichi  Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 研究員 (50439452)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsスフィンゴ脂質 / C型肝炎ウイルス / SPT阻害剤 / 抗HCV剤
Research Abstract

It is reported that hepatitis C virus (HCV) replicated on the lipid raft. We previously demonstrated that sphingomyelin contributed to HCV replication via binding HCV-NS5B (RNA dependent RNA polemerase). Here, we found that other sphingolipids contributed to HCV replication as well as sphingomyelin. Futhermore, we showed that sphingolipids activeted RNA dependent RNA polemerase as well as bound it. Using chimeric mice with humanized livers infected by HCV, we also demonstrated that antiviral effect by SPT inhibitor is corelative to the reduction of sphingolipids in the treated chimeric mice liver, indicating that sphingolipids is essential to HCV replication in vivo. These findings will lead to the development of novel drugs to HCV.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (23 results)

All 2010 2009 2008 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (13 results) Remarks (2 results)

  • [Journal Article] Suppression of hepatitis C virus (HCV) with serine palmitoyltransferase inhibitor.2010

    • Author(s)
      Hirata Y, Sudoh M, Kohara M
    • Journal Title

      Yakugaku Zasshi 130(2)

      Pages: 157-61

    • Related Report
      2009 Final Research Report
  • [Journal Article] Pathogenesis of hepatitis C virus infection in Tupaia belangeri.2010

    • Author(s)
      Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, Hayashi Y, Hishima T, Funata N, Yonekawa H, Kohara M
    • Journal Title

      J Virol. 84(1)

      Pages: 303-11

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of Hepatitis C Virus (HCV) Replication with Serine Palmitoyltransferase Inhibitor2010

    • Author(s)
      Yuichi Hirata
    • Journal Title

      YAKUGAKU ZASSHI 130

      Pages: 157-161

    • NAID

      130000171282

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Pathogenesis of hepatitis C virus infection in Thpaia belangeri.2010

    • Author(s)
      Amako Y, et.al.
    • Journal Title

      Journal of Virology 84

      Pages: 303-311

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol Delta24-reductase.2009

    • Author(s)
      Nishimura T, Kohara M, Izumi K, Kasama Y, Hirata Y, Huang Y, Shuda M, Mukaidani C, Takano T, Tokunaga Y, Nuriya H, Satoh M, Saito M, Kai C, Tsukiyama-Kohara K
    • Journal Title

      J Biol Chem 284(52)

      Pages: 36442-52

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol Delta24-reductase.2009

    • Author(s)
      Nishimura T, et. al.
    • Journal Title

      Journal of biological chemistry 284

      Pages: 36442-36452

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of hepatitis C virus with the reagent targetting host factors2008

    • Author(s)
      Hirata Y, Sudoh M, Kohara M
    • Journal Title

      Uirusu 58(2)

      Pages: 207-13

    • NAID

      10023888598

    • Related Report
      2009 Final Research Report
  • [Journal Article] 宿主因子を標的としたC型肝炎ウイルスの抑制

    • Author(s)
      Yuichi Hirata
    • Journal Title

      ウイルス

    • NAID

      10023888598

    • Related Report
      2008 Annual Research Report
  • [Presentation] A newly synthesized serine palmytoiltransferase inhibitor, NA808, has arobust antiviral effect to hepatitis C virus via hindering host-virus interactions2009

    • Author(s)
      平田雄一
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] A newly synthesized serine palmytoiltransferase inhibitor, NA808, has a robust antiviral effect to hepatitis C virus via hindering host-virus interactions2009

    • Author(s)
      Yuichi Hirata
    • Organizer
      60th Annualmeeting of the American Association for the study of the liver disease
    • Place of Presentation
      USA、ボストン
    • Year and Date
      2009-11-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新規SPT阻害剤NA808の抗HCV効果2009

    • Author(s)
      平田雄一
    • Organizer
      第56回ウイルス学会
    • Place of Presentation
      東京
    • Year and Date
      2009-10-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] A newly synthesized serine palmitoyltransferase inhibitor, NA 808, has the strong effect to hepatitis C virus in vitro and in vivo2009

    • Author(s)
      Yuichi Hirata
    • Organizer
      44th Annualmeeting of the European Association for the study of the liver
    • Place of Presentation
      デンマーク、コペンハーゲン
    • Year and Date
      2009-04-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] A newly synthesized serine palmytoiltransferase inhibitor, NA808, has a robust antiviral effect to hepatitis C virus via hindering host-virus interactions2009

    • Author(s)
      平田雄一
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2009 Final Research Report
  • [Presentation] 新規SPT阻害剤NA808の抗HCV効果2009

    • Author(s)
      平田雄一
    • Organizer
      第57回ウイルス学会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] A newly synthesized serine palmytoiltransferase inhibitor, NA808, has a robust antiviral effect to hepatitis C virus via hindering host-virus interactions.2009

    • Author(s)
      Yuichi Hirata
    • Organizer
      60th Annualmeeting of the American Association for the study of the liverdisease.
    • Place of Presentation
      Boston, USA
    • Related Report
      2009 Final Research Report
  • [Presentation] A newly synthesized serine palmitoyltransferase inhibitor, NA 808, has the strong effect to hepatitis C virus in vitro and in vivo.2009

    • Author(s)
      Yuichi, Hirata
    • Organizer
      44th Annualmeeting of the European Association for the study of the liver
    • Place of Presentation
      Copenhagen, Denmark
    • Related Report
      2009 Final Research Report
  • [Presentation] スフィンゴミエリンはC型肝炎ウイルス複製に必要な脂質成分である2008

    • Author(s)
      平田雄一
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会BMB 2008
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] セリンパルミトリルトランスフェラーゼ(SPT)阻害剤のin vitro及びin vivoにおけるHCV複製抑制効果の検討2008

    • Author(s)
      平田雄一
    • Organizer
      第16回日本消化器病学会関連週間JDDW 2008
    • Place of Presentation
      東京
    • Year and Date
      2008-10-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] スフィンゴミエリンはC型肝炎ウイルス複製に必要な脂質成分である2008

    • Author(s)
      平田雄一
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] SPT阻害剤によるHCV複製阻害機序の解析2008

    • Author(s)
      平田雄一
    • Organizer
      第56回ウイルス学会
    • Place of Presentation
      岡山
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] セリンパルミトリルトランスフェラーゼ(SPT)阻害剤のin vitro及びin vivoにおけるHCV複製抑制効果の検討2008

    • Author(s)
      平田雄一
    • Organizer
      第16回日本消化器病学会関連週間
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.rinshoken.or.jp/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.rinshoken.or.jp/

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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