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Analysis of replication of Hepatitis C Virus using highly efficient replication system

Research Project

Project/Area Number 16590653
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

WAKITA Takaji  Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Senior Research Scientist, 東京都神経科学総合研究所, 副参事研究員 (40280789)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Michiko  Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Scientist, 研究員 (40190821)
KATO Takanobu  Nagoya City University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究科, 助手 (20333370)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsHCV / virus / viral genome replication / HCC / chronic hepatitis / interferon
Research Abstract

Hepatitis C virus (HCV) is a major public health problem, infecting an estimated 170 million people worldwide. Current therapy for HCV-related chronic hepatitis is based on the use of interferon. However, virus clearance rates are insufficient. Investigations to develop the anti-viral therapy or to understand the life cycle of this virus have been hampered by the lack of viral culture systems. We isolated the JFH-1 strain from a patient with fulminant hepatitis, and the JFH-1 subgenomic replicon could replicate efficiently in culture cell without adaptive mutation. Using this JFH-1 strain, we developed highly efficient HCV replication system in culture cells. The full-length JFH-1 RNA was transfected into Huh7 cells. Subsequently, viral RNA efficiently replicated in transfected cells and viral particles were secreted. Secreted viral particle exhibited spherical shape by electron-microscopic analysis and was separated in the fraction eith 1.15g/ml density. Furthermore, secreted virus displayed infectivity for naive Huh7 cells. In addition, we have also developed an replicon system using full-genomic JFH-1 genome. Both systems provide powerful tools for studying the viral life cycle and constructing anti-viral strategies.

Report

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

    (40 results)

All 2006 2005 2004

All Journal Article (40 results)

  • [Journal Article] Characterization of Genotype 2a Hepatitis C Virus Subgenomic Replicon in Comparison with Genotype 1b Replicon2006

    • Author(s)
      M Miyamoto, et al.
    • Journal Title

      Intervirology 49

      Pages: 37-43

    • 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] Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cell2006

    • Author(s)
      Yi M, et al.
    • Journal Title

      Proc Natl Acad Sci USA 103(7)

      Pages: 2310-5

    • 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] Generation of infectious hepatitis C virus in immortalized human hepatocytes.2006

    • Author(s)
      T Kanda, A Basu, R Steele, T Wakita, JS.Ryerse, R Ray, RB Ray.
    • Journal Title

      Journal of 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] Characterization of the replication sensitivity to cyclosporin A among strains of hepatitis C virus2006

    • Author(s)
      N Ishii, K Watashi, T Hishiki, K Goto, D Inoue, M Hijikata, T Wakita, N Kato, K Shimotohno
    • Journal Title

      Journal of 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] Subcellular localization of hepatitis C virus structural proteins in a cell culture system that efficiently replicates the virus.2006

    • Author(s)
      Y Rouille, F Helle, D Deigrange, P Roingeard, C Voisset, E Blanchard, S Belouzard, J McKeating, A Patel, G Maertens, T Wakita, C Wychowski, J Dubuisson
    • Journal Title

      Journal of 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] Production of infectious genotype is hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells.2006

    • Author(s)
      Yi M, Villanueva RA, Thomas DL, Wakita T, Lemon SM.
    • Journal Title

      Proc Nat Acad Sci USA. 103(7)

      Pages: 2310-2316

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of Genotype 2a Hepatitis C Virus Subgenomic Replicon in Comparison with Genotype 1b Replicon.2006

    • Author(s)
      M Miyamoto, T Kato, T Date, M Mizokami, T Wakita.
    • Journal Title

      Intervirology 49

      Pages: 37-43

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Non-Hepatic Cell Lines HeLa and 293 Cells Support Efficient Replication of Hepatitis C Virus Genotype 2a Subgenomic Replicon.2005

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

      Journal of Virology 79

      Pages: 592-596

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nuclear Localization of Japanese Encephalitis Virus Core Protein Enhances Viral Replication2005

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

      Journal of Virology 79

      Pages: 3448-58

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterisation of the E-138 (Glu/Lys) mutation in Japanese encephalitis virus using a stable full-length infectious cDNA clone2005

    • Author(s)
      Zhao Z, et al.
    • Journal Title

      Journal of General Virology 86

      Pages: 2209-2220

    • 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] Production of Infectious Hepatitis C Virus in Tissue Culture from a Cloned Viral Genome2005

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

      Nature Medicien 11

      Pages: 791-796

    • 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] Robust Hepatitis C Virus Infection in Vitro2005

    • Author(s)
      J Zhong, et al.
    • Journal Title

      Proc Natl Acad Sci USA 102

      Pages: 9294-9299

    • 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] Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfeted humanhepatoma cells2005

    • Author(s)
      Cai Z, et al.
    • Journal Title

      Journal of Virology 79

      Pages: 13963-73

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Detection of Anti-Hepatitis C Virus Effects of Interferon and Ribavirin by Sensitive Replicon System2005

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

      Journal of Clinical Microbiology 43

      Pages: 5679-84

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 遺伝子型2aのC型肝炎ウイルス(HCV)由来のRNAレプリコン2005

    • Author(s)
      脇田隆字
    • Journal Title

      バイオテクノロジージャーナル 5(3)

      Pages: 300-2

    • 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] 宿主の新たな抗ウイルス活性によるB型肝炎ウイルス複製の抑制2005

    • Author(s)
      脇田隆字
    • Journal Title

      Hepatoday 9

      Pages: 6-7

    • 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] 感染性C型肝炎ウイルス粒子の培養細胞における作製2005

    • Author(s)
      脇田隆字
    • Journal Title

      医学のあゆみ 215(11)

      Pages: 920-1

    • 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] C型肝炎ウイルス培養細胞感染系の確立2005

    • Author(s)
      加藤孝宣, 他
    • Journal Title

      ウイルス 55(2)

      Pages: 287-296

    • NAID

      10017102684

    • 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] HCVレプリコン2005

    • Author(s)
      脇田隆字
    • Journal Title

      肝臓 46(12)

      Pages: 691-702

    • NAID

      10020605421

    • 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] Detection of Anti-Hepatitis C Virus Effects of Interferon and Ribavirin by a Sensitive Replicon System2005

    • Author(s)
      T Kato, T Date, M Miyamoto, M Sugiyama, Y Tanaka, E Orito, T Ohno, K Sugihara, I Hasegawa, K Fujiwara, K Ito, A Ozasa, M Mizokami, T Wakita.
    • Journal Title

      Journal of Clinical Microbiology 43

      Pages: 5679-5684

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfeted humanhepatoma cells.2005

    • Author(s)
      Cai Z, Zhang C, Chang K-Y, Jiang J, Ahn B-C, Wakita T, Liang, JT, Luo G.
    • Journal Title

      Journal of Virology. 79

      Pages: 13963-13973

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Robust Hepatitis C Virus Infection in Vitro2005

    • Author(s)
      J Zhong, P Gastaminza, G Cheng, S Kapadia, T Kato, DR Burton, SF Wieland, S Uprichard, T Wakita, FV Chisari
    • Journal Title

      PNAS 2005 102

      Pages: 9294-9299

    • 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 in Tissue Culture from a Cloned Viral Genome2005

    • Author(s)
      T Wakita, T Pietschmann, T Kato, T Date, M Miyamoto, Z Zhao, K Murthy, A Habermann, H-G Krausslich, M Mizokami, R Bartenschlager, T J Liang
    • Journal Title

      Nat Med. 11

      Pages: 791-796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterisation of the E-138 (Glu/Lys) mutation in Japanese encephalitis virus using a stable full-length infectious cDNA clone2005

    • Author(s)
      Zhao Z, Date T, Li Y, Kato T, Miyamoto M, Yasui K, Wakita T.
    • Journal Title

      J.Gen.Virol. 86

      Pages: 2209-2220

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nuclear Localization of Japanese Encephalitis Virus Core Protein Enhances Viral Replication2005

    • Author(s)
      Y Mori, T Okabayashi, T Yamashita, Z Zhao, T Wakita, K Yasui, F Hasebe, M Tadano, E Konishi, K Moriishi, Y Matsuura.
    • Journal Title

      J Virol. 79

      Pages: 3448-3458

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Non-Hepatic Cell Lines HeLa and 293 Cells Support Efficient Replication of Hepatitis C Virus Genotype 2a Subgenomic Replicon.2005

    • Author(s)
      T Kato, T Date, M Mivamoto, Z Zhao, M Mizokami, T Wakita
    • Journal Title

      J Virol 79

      Pages: 592-596

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Robust production of infectious hepatitis C virus(HCV) from stably HCV cDNA-transfeted humanhepatoma cells2005

    • Author(s)
      Cai Z, et al.
    • Journal Title

      Journal of General Virology 79

      Pages: 13963-13973

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Detection of Anti-Hepatitis C Virus Effects of Interferon and Ribavirin by a Sensitive Replicon System2005

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

      Journal of Clinical Microbiology 43

      Pages: 5679-5684

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Non-Hepatic Cell Lines HeLa and 293 Cells Support Efficient Replication of Hepatitis C Virus Genotype 2a Subgenomic Replicon.2005

    • Author(s)
      T Kato, T Date, M Miyamoto, Z Zho, M Mizokami, T Wakita
    • Journal Title

      Journal of Virology 79

      Pages: 592-596

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nuclear Localization of Japanese Encephalitis Virus Core Protein Enhances Viral Replication2005

    • Author(s)
      Y Mori, T Okabayashi, T Yamashita, Z Zhao, t Wakita, et al.
    • Journal Title

      Journal of Virology 79

      Pages: 3448-3458

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genotype 2a Hepatitis C Virus Subgenomic Replicon Can Replicate in HepG2 and IMY-N9 cells2004

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

      Journal of Biological Chemistry 279

      Pages: 22371-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Hepatitis C Virus Replication by Interferon Regulatory Facctor-12004

    • Author(s)
      Kanazawa N, et al.
    • Journal Title

      Journal of Virology 78

      Pages: 9713-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Difference of Hepatitis C Virus Core Protein Processing between Genotypes 1 and 2.2004

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

      Hapatology Research 30

      Pages: 204-209

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HCV repliconに関する研究2004

    • Author(s)
      脇田隆字
    • Journal Title

      臨床消化器内科 19

      Pages: 1545-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] HCV repliconによるHCV RNA複製2004

    • Author(s)
      脇田隆字
    • Journal Title

      細胞 36・7

      Pages: 293-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Difference of Hepatitis C Virus Core Protein Processing between Genotypes 1 and 2.2004

    • Author(s)
      T Kato, M Miyamoto, T Date, A Furusaka, M Mizokami, T Wakita
    • Journal Title

      Hepatology Research 30

      Pages: 204-209

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Regulation of Hepatitis C Virus Replication by Interferon Regulatory Facctor-12004

    • Author(s)
      Kanazawa N, Kurosaki M, Sakamoto N, Enomoto N, Itsui Y, Yamashiro T, Tanabe Y, Maekawa S, Nakagawa M, Chen C-H, Oshima S, Nakamura T, Kato T, Wakita T, Watanabe M
    • Journal Title

      J Virol 78

      Pages: 9713-9720

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genotype 2a Hepatitis C Virus Subgenomic Replicon Can Replicate in HepG2 and IMY-N9 cells2004

    • Author(s)
      Date T, Kato T.Mivamoto M, Zhao Z, Yasui K, Mizokami M, Wakita T.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 22371-22376

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genotype 2a Hepatitis C Virus Subgenomic Replicon Can Replicate in HepG2 and IMY-N9 cells2004

    • Author(s)
      Date T, Kato T, Miyamoto M, Zhao Z, Yasui K, Mizokami M, Wakita T
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 22371-22376

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of Hepatitis C Virus Replication by Interferon Regulatory Facctor-12004

    • Author(s)
      Kanazawa N, Kurosaki M, Sakamoto N, et al.
    • Journal Title

      Journal of Virology 78

      Pages: 9713-9720

    • Related Report
      2004 Annual Research Report

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

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