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Determination of host factor for hepatitis C virus replication

Research Project

Project/Area Number 16390139
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

KOHARA Michinori  Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Head, 東京都臨床医学総合研究所, 副参事研究員 (10250218)

Co-Investigator(Kenkyū-buntansha) SHUDA Masahiro  Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (10356256)
TAKAHASHI Nobuhiro  Tokyo University of Agriculture and Technology, Professor, 応用生物科学科, 教授 (80293017)
INOUE Kazuaki  Showa University, Assistant Professor, 医学部, 助教授 (90232529)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsCyclosporin A / Cyclophilin / Hepatitis C virus / Genome replication / Replication inhibitor / 宿主因子
Research Abstract

Hepatitis C virus is the most common cause of chronic liver disease. However, the efficacy of currently available treatments is limited. We recently reported the effects of combined interferon-a/cyclosporin A treatment. In the present study, we examined the effects and mechanism of cyclosporin A on HCV replication.
We evaluated the effect of cyclosporin A on the replication of HCV in vitro. The gene expression of three representative cyclophilins (A, B and F) and Pin-1 were knocked down using small interfering RNAs to clarify which cyclophilin(s) is associated with HCV RNA replication.
Interferon-a combined cyclosporin A treatment accelerated the rate of reduction in serum HCV RNA compared to interferon monotherapy. Cyclosporin A and other inhibitors of the peptidyl-prolyl cis-trans isomerase activity of cyclophilins inhibited HCV RNA replication in HCV replicon cells and in a cell culture system. In contrast, FK506 did not have any inhibitory effect on HCV RNA replication.
These findings indicate that cyclophilins are a crucial component of HCV RNA replication in vitro. Furthermore, cyclophilin B, cyclophilin F and other members of the cyclophilins appear to be involved in HCV RNA replication in vitro. Cyclophilins are essential for HCV RNA replication in vitro, and thus their potent inhibitors are promising anti-HCV drugs.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (28 results)

All 2006 2005 2004

All Journal Article (26 results) Book (2 results)

  • [Journal Article] Intracellular-diced dsRNA has enhanced efficacy for silencing HCV RNA and overcomes variation in the viral genotype.2006

    • Author(s)
      Watanabe, T.
    • Journal Title

      Gene Theraphy (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Pre-treatment prediction of interferon-aefficacy in chronic hepatitis C patients2006

    • Author(s)
      Hayashida, K.
    • Journal Title

      Clinical Gastroenterology and Hepatology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Feeze-dried formulations for in vivo gene delivery of PEGylated polyplex micelles with disulfide crosslinked cores to the liver2006

    • Author(s)
      Miyata, K.
    • Journal Title

      Journal of Controlled Release (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Serine palmitoyltransferase inhibitor suppresses HCV replication in a mouse model.2006

    • Author(s)
      Takuya Umehara, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immune complex of hepatitis C virus particles detected by immunogold electron microscopy.2006

    • Author(s)
      Masahiko Kaito, et al.
    • Journal Title

      J.Gastroenterology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b.2006

    • Author(s)
      Kyoko Murakami, et al.
    • Journal Title

      Virology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Targeting the Hepatitis C Virus genome with RNA interference using highly effective and non-toxic long double-stranded RNA.2006

    • Author(s)
      Tsunamasa Watanabe, et al.
    • Journal Title

      Gene Theraphy 13

      Pages: 883-892

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Freeze-dried formulations for in vivo gene delivery of PEGylated polyplex micelles with disulfide crosslinked cores to the liver.2006

    • Author(s)
      Yoshinori Kakizawa, et al.
    • Journal Title

      Journal of Controlled Release 109

      Pages: 15-23

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Freeze-dried formulations for in vivo gene delivery of PEGylated polyplex micelles with disulfide crosslinked cores to the liver2006

    • Author(s)
      Miyata, K.
    • Journal Title

      Journal of Controlled Release (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rational design of dual-functional aptamers that inhibit protease and helicase activities of HCV NS3.2005

    • Author(s)
      Umehara, T.
    • Journal Title

      Journal of Biochemistry 137

      Pages: 339-347

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of hypervariable region in hepatitis c virus envelope protein during acute and chronic infection.2005

    • Author(s)
      Higashi, K.
    • Journal Title

      Arch. Virology 150(5)

      Pages: 883-898

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Host sphingolipid biosynthesis as a target for hepatitis C virus therapy.2005

    • Author(s)
      Sakamoto, H.
    • Journal Title

      Nature Chemical Biology 1

      Pages: 333-337

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Host sphingolipid biosynthesis as a target for hepatitis C virus therapy.2005

    • Author(s)
      Hiroshi Sakamoto, et al.
    • Journal Title

      Nat.Chem.Biol. 1

      Pages: 333-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pre-treatment Prediction of Interferon-a efficacy in chronic hepatitis C patients.2005

    • Author(s)
      Kazuhiro Hayashida, et al.
    • Journal Title

      Clinical Gastroenterology and Hepatology 3

      Pages: 1253-1259

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rational design of dual-functional aptamers that inhibit protease and helicase activities of HCV NS3.2005

    • Author(s)
      Takuya Umehara, et al.
    • Journal Title

      J.Biochemistry 137

      Pages: 339-347

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rational design of dual-functional aptamers that inhibt protease and helicase activities of HCV NS3.2005

    • Author(s)
      Umehara, T.
    • Journal Title

      Journal of Biochemistry 137

      Pages: 339-347

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characterization of hypervariable region in hepatitis c virus envelope protein during acute and chronic infection.2005

    • Author(s)
      Higashi, K.
    • Journal Title

      Arch.Virology 150(5)

      Pages: 883-898

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Membrane Binding Properties and Terminal Residues of the Mature 1 HCV Capsid Protein in Insect Cells.2004

    • Author(s)
      Tomoaki Ogino, et al.
    • Journal Title

      J.Virology 78(21)

      Pages: 11766-11777

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Major Histocompatibility Complex Class-I Presentation Impaired by Hepatitis C Virus on Dendritic Cells During Maturation.2004

    • Author(s)
      Yoichi Hiasa, et al.
    • Journal Title

      J.Med.Virol. 74(2)

      Pages: 253-261

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation of the CKI-cdk-Rb-E2F Pathway in Full-Genome Hepatitis C Virus Expressing Cells.2004

    • Author(s)
      Kyoko Tsukiyama-Kohara, et al.
    • Journal Title

      J.Biol.Chem 279

      Pages: 14531-1451

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Virological significance of low-level hepatitis B virus infection in patients with hepatitis C virus associated liver disease.2004

    • Author(s)
      Tanaka, T
    • Journal Title

      J.Medical Virology 72

      Pages: 223-229

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone.2004

    • Author(s)
      Maeda, N
    • Journal Title

      Liver International 24

      Pages: 259-267

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activation of the CKI-cdk-Rb-E2F pathway in full-genome hepatitis C virus expressing cells.2004

    • Author(s)
      Tsukiyama-Kohara, K
    • Journal Title

      J.Biol.Chem 279(15)

      Pages: 14531-14541

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A low-density cDNA microarray with a unique reference RNA : pattern recognition analysis for IFN efficacy prediction to HCV as a model.2004

    • Author(s)
      Daiba, A
    • Journal Title

      Biochem.Biophys.Res.Commun. 315

      Pages: 1088-1096

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Major histocompatibility complex class-I presentation impaired by hepatitis C virus on dendritic cells during maturation.2004

    • Author(s)
      Hiasa, Y
    • Journal Title

      J.Med.Virol 74(2)

      Pages: 253-261

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Membrane binding properties and terminal residues of the mature HCV capsid protein in insect cells.2004

    • Author(s)
      Ogino, T
    • Journal Title

      J.Virology 78(21)

      Pages: 11766-11777

    • Related Report
      2004 Annual Research Report
  • [Book] RNAiによるC型肝炎ウイルス治療戦略2005

    • Author(s)
      渡邊 綱正
    • Total Pages
      5
    • Publisher
      細胞工学
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Book] 内科2004

    • Author(s)
      井上和明
    • Total Pages
      6
    • Publisher
      南江堂
    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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