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1998 Fiscal Year Final Research Report Summary

A study on the interferon-resistancy of hepatits C virus

Research Project

Project/Area Number 08457164
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SATO Chifumi  Tokyo Medical and Dental University, Faculty of Medicine, Professor, 医学部, 教授 (60154069)

Co-Investigator(Kenkyū-buntansha) KUROSAKI Masayuki  Tokyo Medical and Dental University, Faculty of Medicine, Assistant, 医学部, 助手 (10280976)
ENOMOTO Nobuyuki  Tokyo Medical and Dental University, Faculty of Medicine, Assistant, 医学部, 助手 (20251530)
Project Period (FY) 1996 – 1998
KeywordsHepatitis C virus / Interferon / Chronic hepatitis
Research Abstract

Previously, we showed that mutations in the NS5A region are closely assiciated with interferon efficacy in hepatitis C virus (HCV) genotype lb infection. In the present study, we studied the relation between interferon efficacy and NSSA mutations in genotype 2 infection. The rate of complete responses was 60% and 30% in genotype 2a and 2b infection, respectively. In both genotypes, there was a positive correlation between the number of mutations in the NS5A region and the response rate to interferon.
The 5'untranslated region (5'UTR) of HCV genome is highly conserved, and serves as an internal ribosomal entry site that initiates the cap-independent translation of HCV polyprotein. Mutations in the 5'UTR has been shown to cause changes in the efficiency of protein translation in vitro. However, the significance of genetic variations of the 5'UTR is not fully known in clinical settings. Therefore, we studied the relation between interferon efficacy and mutatinas in the 5'UTR.Sequence varia … More blilty of the 5'UTR had no influence on inteiferon efficacy or serum HCV-RNA concentrations in clinical settings. These results indicate that diverse clinical pictures among patients with a given genotype of HCV could not be explained by the sequence variability seen in the 5'UTR that is thought to have a key role in both HCV-RNA replication and translation. So far, the NS5A region is considered to be the only site that is associated with interferon efficacy.
To study the mechanism of the difference in interferon sensitivity of the NS5A region, we investigated the transcriptional activation function of the NS5A region and the effect of amino acid mutations in the NS5A region. The NS5A region had a transcriptional activity and it was enhanced by amino acid mutations, which are also related to decreased viral load and increased interferon sensitivity. We then studies the effect of NS5A on the interferon signal transduction system. The NS5A protein of HCV inhibited cellula responses to IFN.This inhibitory effect was more prominent in the wild type NS5A than the mutant type. These observations indicate that the repression of IFN signal transduction pathway by the NS5A protein may be one of the mechanisms through which HCV confers resistance to TEN. Less

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Yamamoto,C.: "Nucleotido sequence varrations in the internal pebosame entry sile of hepatitisevirus-1b :no association with efficacy of interferon therapyor serun HCV-RNA leiols" Hepatology. 26. 1616-1620 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuwa,T: "Mutation in the interferon-sensitivity clekrmining region of hepatitis C virus and transcriptional activity of the nonstructural region 5A protein" Hepatology. 28. 1147-1153 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chikara Yamamoto: "Nucleotide sequence variation in the internal rebosome entry site of hepatitis C virus-1b : noassociation with efficacy of interferon therapy or serumHCV-RNA levels." Hepatology. 26. 1616-1620 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshiko Fukuma: "Mutations in the interferon-sensitivity determining region of hepatitis Cvirus and transcriptional activity of the nonstructural region 5A protein." Hepatology. 28. 1147-1153 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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