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Molecular analysis on the tumorigenicity of hepatitis C virus nonstructural protein NS3

Research Project

Project/Area Number 08670352
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKanazawa Medical University

Principal Investigator

TAKEGAMI Tsutomu  Kanazawa Medical University Medical Research Institute Associate Professor, 総合医学研究所, 助教授 (10113490)

Co-Investigator(Kenkyū-buntansha) NOJIMA Takayuki  Kanazawa Medical University Department of Pathology Professor, 医学部, 教授 (50142732)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHepatitis C virus / Nonstructural protein NS3 / Transformation / Tumorigenicity / p53 / Flavivirus / Antiviral drug / p53 / ウイルス蛋白NS3 / GST-NS3融合蛋白
Research Abstract

In order to examine the influence of hepatitis C virus (HCV) NS3 to the cells, we used transfection method using lipofectin. Transfectant containing 5'half sequence of the HCV genome segment encoding NS3 (HCV-NS3-N) rapidly proliferated and formed tumors in nude mice. However, after the cotransfection with tumor suppressor gene p53 transfectants (HCV-NS3-N+p53) did not show any tumorigenicity. The result suggest that HCV-NS3 has some influence to the function of p53. To investigate the interaction between HCV-NS3 and p53, we prepared the fusion-protein GST-HCV-NS3 expressed in the bacteria. In the binding experiment in vitro using cell extracts, we did not detect the binding of NS3 to p53. This does not exclude the possibility of the weak or indirect interaction between HCV-NS3 and p53. Actually we found 90 kDa protein which could bind to HCV-NS3. On the other hand, we tried to find the effective antiviral drug using the replication system of HCV-related virus, i.e. Japanese encephalitis virus (JEV). One of tested reagents, furanonaphtoquinone (FNQ) showed antiviral activity (Takegami et al., 1998). To retard the tumorigenesis by HCV,it is important to inhibit viral replication and some reactions between virus and host cells. Further analyzes on the interaction of HCV-NS3 and host proteins including p53, and mechanism of antiviral effect of FNQ are essential.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] T.Takegami: "Inhibitory effect of furanonaphthoquinone derivatives on the replication of Japanese encephalitis virus" Antiviral Res.37(1). 34-45 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 竹上 勉: "C型肝炎ウイルス非構造蛋白質NS3領域遺伝子の導入による細胞の形質転換:マウス線維芽細胞株NIH3T3とヒト肝細胞由来株HepG2及びKN73との比較" 金沢医大総医研年報. 7. 117-124 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 竹上 勉: "フラビウイルスの遺伝子発現および細胞との相互作用" ウイルス. 46(2). 91-97 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 竹上勉: "肝臓フォーラム'96記録集 HCVの発癌性" 医事出版社, 179(61--67) (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 竹上勉: "肝炎・肝硬変・肝癌(小俣政男編)C型肝炎ウイルスcarcinogenesis" 羊土社, 193(166-167) (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takegami: "Inhibitory effect of furanonaphthoquinone derivatives on the replication of Japanese encephalitis virus" Antiviral Res.37(1). 37-45 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takegami: "Flavivirus RNA replication and involvement of host factors (in Japanese)" Virus. 46(2). 91-97 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Takegami: "Inhibitory effect of furanonaphthoquinone derivatives on the replicatoin of Japanese encephalitis virus" Antiviral Res.37(1). 37-45 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 竹上勉: "C型肝炎ウイルス非構造蛋白質NS3領域遺伝子の導入による細胞の形質転換:マウス繊維芽細胞株NIH3T3とヒト肝細胞由来株HepG2及びKN73との比較" 金沢医大総医研年報. 7. 117-124 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 竹上勉: "フラビウイルスの遺伝子発現および細胞との相互作用" ウイルス. 46(2). 91-97 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 竹上勉: "肝臓フォーラム'96記録集 HCVの発癌性" 医事出版社, 61-67(179) (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 竹上勉: "肝炎・肝硬変・肝癌(小俣政男編)C型肝炎ウイルスcarcinogenesis" 羊土社, 166-167(193) (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 竹上勉: "C型肝炎ウイルス非構造蛋白質NS3領域遺伝子の導入による細胞の形質転換" 金沢医大総医研年報. 7. 117-124 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 野島孝之: "分子生物学的解析により確診した滑膜肉腫の一例" 病院病理. 14(1). 48 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kazuya,Annen: "Analysis of the hepatocyte growth factor receptor in regeneration and oncogenesis of the liver." Gen. Diagn. Pathol. 141. 171-186 (1995/1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 竹上勉: "フラビウイルスの遺伝子複製および細胞との相互作用" ウイルス. 46(2). 91-97 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 竹上勉: "肝炎・肝硬変・肝癌 分子メカニズムから病態診断治療まで(分担・C型肝炎ウイルスcarcinogenesis166-167)" 羊土社 小俣政男編, 193 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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