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ANALYSIS OF MUTATIONS IN HEPATITIS B VIRUS ENHANCER 2/CORE PROMOTER ANT THEIR FUNCTIONAL ROLES IN HEPATITIS B

Research Project

Project/Area Number 06670521
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionCHIBA UNIBERSITY

Principal Investigator

YOKOSUKA Osamu  CHIBA UNIVERSITY,UNIV HOSPITAL,LECTURER, 医学部, 講師 (90182691)

Co-Investigator(Kenkyū-buntansha) EHATA Toshiki  CHIBA UNIVERSITY,UNIV HOSPITAL,ASSISTANT, 医学部附属病院, 助手
IMAZEKI Fumio  CHIBA UNIVERSITY,UNIV HOSPITAL,ASSISTANT, 医学部附属病院, 助手 (40223325)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsHepatitis B virus / HBV-DNA / Enhancer 2 / Core promoter / CAT actiity / B型肝炎ウイルス / HBV‐DNA / コアプロモーター
Research Abstract

The mechanism of liver diseases by hepatitis B virus is still unknown. Several studies have suggested that the hepatitis B core antigen peptides could be the immunological targets of cytotoxic T lymphocytes. Enhancer 2/ core promoter regions are thougth to have close relationship to the expression of the core peptides. We examined the mutations in these regions which may be related to type B hapatitis. The entire nucleotide sequence from enhancer 2/ core promoter regions were investigated by direct sequencing of the amplified products derived from 40 patients with HBV infection. In enhancer 2/ core promoter region, there were 11 nucleotide mutations in 9 asymptomatic carriers (1.2/case) and 73 in 17 chronic hepatitis patients (4.3/case) , 4 mutations in 4 acute hepatitis (1.0/case) , 11 in 4 fulminant hepatitis, 25 in 6 fatal acute exacerbations. The most frequent substitutions were recognized at nt. 1764 and at nt. 1766. Thses mutation in enhancer 2/core promoter region were considered to be an important site fore core promoter function. There was no difference in enhancer activity between the sequences with or without mutation.
These data suggest that mutations in the enhancer 2/core promoter region could affect the expression of the precore message and might have influence in the pathogenesis of type B hepatitis.

Report

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

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Yokosuka Osamu: "Efficacy of longterm inferferon freatment in chromic liver disease evaluated by sensitive PCR assay for HCVRNA." Gut. 37. 721-726 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakahori Susumu: "Detection of hepatitis B evirus precore stop codon mutants by selective amplification method." J.Gastroenterology & Hepatology. 10. 419-425 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tagawa Masami: "Infection of human hepatocyte cell lines with hepatitis C virus in vitro" J.Gastroenterolog & Hepatology. 10. 523-527 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Honda Arata: "Detection of mutants in the enhancer z/core promoter region in patients with chronic HBV infection." Hepatology. (投稿中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yokosuka O,Kato N,Hosoda K,Ito Y,Imazeki F,Ohto M,Omata M.: "Efficacy of longterm interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA." Gut. 37. 721-726 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nakahori S,Yokosuka O,Ehata T,Chuang W-L,Imazeki F,Ito Y,Ohto M.: "Detection of hepatitis B virus precore stop codon mutants by selective amplification method." J Gastroenterol Hepatol. 10. 419-425 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tagawa M,Kato N,Yokosuka O,Ishikawa T: "Infection of human hepatocyte cell lines with hepatitis C virus in vitro." J Gastroenterol Hepatol. 10. 523-527 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Honda A,Yokosuka O,Ehata T,Imazeki F, Tagawa M.: "Detection of mutations in the enhancer 2/core promoter and pre-C,core region in patients with chronic hepatitis B virus infection." Hapatology. (in submission).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yokosuka Osamu: "Efficag of longterm IFN in CLD eualnoted by sensifiue PCR for HCD RNA." Gut. 37. 721-726 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakahori Susumu: "Detection of HBV precone stop codon mutation by seledie anplification method." J. Gastroenterology & Hepatology. 10. 419-425 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tagawa Masami: "Infection of human cell lines with Repafrfis C oirus in vitro" J. Gastroenterology & Hepatology. 10. 523-527 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 本田新 ほか: "B型劇症肝炎及び慢性肝炎急性増悪死亡例におけるHBV enhancerIIの変異の検討" 肝臓. 35. S(I)277 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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