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Interferon resistance of hepatitis C virus

Research Project

Project/Area Number 06670595
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOkinaka Memorial Institute for Medical Study

Principal Investigator

CHAYAMA Kazuaki  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (00211376)

Co-Investigator(Kenkyū-buntansha) IKEDA Kenji  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (80211027)
KUMADA Hiromitsu  Research associate Okinaka Memorial Institute for Medical Research, 研究員 (20124307)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
KeywordsHepatitis C virus / amino acid sequence / ISDR / PCR / C型肝炎ウイルス / インターフェロン
Research Abstract

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are prdictive factors of poor response to interferon therapy in patients with chronic hepatitis C.However, few patients with low virus load and genotype 1b show poor response to treatment. To further examine the factors predicting the response to interferon therapy in patients with genotype 1b infection, we analyzed entire nucleotide sequences of HCV extracted from three non-responders and one responder. We were no able to identify any single amino acid mutation which determines the resitance to interferon. We also examined 57 consecutive patients who were treated with 624 million units of lymphoblastoid alpha-interferon. Multivariate analysis showed that pretreatment virus load and multiple amino acid substitutions in the ISDR significantly correlated with failure to eliminate the virus. Our data support the hypothesis that HCV without amino acid substitution in the ISDR is resistant to interferon treatment. However, polymerase chain reaction-based analysis of two responders with multiple amino acid substitutions in the ISDR revealed the presence of a small amount of wild type strain in their serum, suggesting that the wild type HCV is not resistant to interferon. The precise mechanism of anti-viral effect of interferon and its relationship with amino acid substitutions of the ISDR should be further investigated in order to develop a more effective anti-viral strategy.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Chayama K et al.: "A pilot study of corticosteroid priming for lymphoblastoid IFN in patients with chronic hepatitis C." Hepatology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "Genotype, slow decrease in virus titer during IFN treatment and high degree of sequence variability of HVR are indicative of poor response to IFN treatment" Journal of Hepatology. 23. 648-653 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "Nucleotide sqquence of hepatitis C virus (type 3b)isolated from a Japanese patient with chronic hepatitis C" Journal of General Virology. 75. 3623-3628 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hashimoto M et al.: "Genotyping of hepatitis C virus by polymerase chain reaction : a comparison of two PCR-based methods using core or NS5 primers." International Hepatology Communications. 4. 67-71 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "High virus titer, slow virus decrease, genotype II, and sequence variability of E2/NS1 HVR predict poor response to interferon therapy in chronic hepatitis C" Viral Hepatitis and Liver Dsease. 617-620 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "A pilot study of corticosteroid priming for lymphoblastoid interferon-alpha in patients with chronic hepatitis C." Hepatology. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "Genotype, slow decrease in virus titer during interferon treatment and high degree of sequence variability of HVR are indicative of poor response interferon treatment" Journal of Hepatology. 23. 648-653 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hashimoto M et al.: "Genotyping of hepatitis C virus by polymerase chain reaction : a comparison of two PCR-based methods using core or NS5 primers" International Hepatology Communications. 4. 67-71 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "Molecular analysis of intraspousal transmission of hepatitis C virus." Journal of Hepatology. 22. 431-439 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "Nucleotide sequences of hepatitis C virus (type 3b) isolated from a Japanese patient wich chronic hepatitis C." Journal of General Virology. 75. 3623-3628 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "Antiviral effect of lymphoblastoid interferon-alpha on hepatitis C virus in patients with chronic hepatitis type C." Journal of Gastroenterology and Hepatology. 9. 128-133 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Chayama K et al.: "A pilot study of corticosteroid priming for lymphoblastoid interferon-alpha in patients with chronic hepatitis C" Hepatology. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chayama K et al.: "Genotype, slow decrease in vrus titer during IFN treatment and high degree of sequence variability of HVR are indicative...." Journal of Hepatology. 23. 648-653 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hashimoto M et al.: "Genotyping of hepatitis C virus by polymerase chain reaction : a comparison of two PCR-based methods using core and NS5 primers." International Hepatology Communications. 4. 67-71 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chayama K et al.: "Nucleotide sequence of hepatitis C virus (type 3b)isolated from a Japanese patient wich chronic hepatitis C." Journal of General Virology. 75. 3623-3628 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chayama K et al.: "Molecular analysis of intraspousal transmission of hepatitis C virus." Journal of Hepatology. 22. 431-439 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chayama K et al.: "Antivira effect of lymphoblastoid interferon-alpha on hepatitis C virus in patients with chronic hepatitis type C." Journal of Gastroenterology and Hepatology. 9. 128-133 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Chayama k et al.: "Antiviral effecf of Iymphoblastoid IFN-alpha on hepa titis C vinus in patients with chronic hepa titis type C" Journal of Gastroenterology and Hepatology. 9. 128-133 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chayama k et al: "Nucleotide Seauence of Hepatitis C virus(type 3b)isolated from a Japanese patient" Journal of Genaral Vtrology. 75. 3623-2628 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chayama k et al: "Slou decrease in virus titer during interferon treatment and hight degree of seguence variability of hyperveriable response to interferon trentment in patients with chronic region are indicative of poor hepat" Journal of Hepatology. in press (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chayama k et al: "Molecular Analysis of Intraspousal,Transmission of Hepatitis C" Journal of Hepatology. in press (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 茶山一彰,他: "C型肝炎ウイルスのgenotype、hypervariable regionのアミノ酸の変異/血清中のウイルス量とインターフエロン" 肝臓. 35. (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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