• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1997 Fiscal Year Final Research Report Summary

Mechanism of Viral Liver Injury by analyzing escape mutant virus and HLA-binding viral peptide

Research Project

Project/Area Number 06404029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionUniversity of Tokyo

Principal Investigator

OMATA Masao  University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (90125914)

Co-Investigator(Kenkyū-buntansha) KATO Naoya  University of Tokyo, Faculty of Medicine, Staff, 医学部・附属病院, 医員
MATSUMURA Masayuki  Asahi Life Foundation Institute for Adult Diseases Department of Gastroenterolog, 消化器科, 部長
SHIRATORI Yasushi  University of Tokyo, Faculty of Medicine, Associate Professor, 医学部・附属病院, 講師 (70196624)
Project Period (FY) 1994 – 1997
Keywordshepatitis B virus (HBV) / HLA / cytotoxic T cell / T cell receptor / YMDD motif / hepatitis C virus (HCV) / NS5A / transcriptional activator
Research Abstract

Hepatitis B virus (HBV)
We purified HLA-binding peptides from HBV stably-transfected human hepatoma cells (HepG2 2.2.15) by affinity chromatography using monoclonal Ab. Amino acid sequence of HLA-binding peptide was determined as NPLPOLPO by HPLC-mass spectrometry (LC/MS/MS).
Full-length HBV DNAs obtained from sera of patients with type B-chronic liver diseases were sequenced Amino acid substitutions were accumulated in core-region and pre-S region according to the progression of chronic liver disease.
The repertoire of T cell receptor alpha-chain of liver-invaded cytotoxic T cells in patiens with type B-chronic active hepatitis, was determined by inverse PCR,cloning and sequencing. The Valpha 7.2 gene was most frequently observed and found to bind Jalpha 33 gene.
We established one-step amplification of 3.2 kbp of full-length HBV DNA by using long-PCR method. Cloned full-length HBV DNA was confirmed to replicate by transfection into human hepatoma cells (Huh7). We made 7 variants by substituting the methionine of the YMDD motif with Ile, Val, Ala, Leu, Lys, Arg and Thr, to explore replication ability and lamivudine sensitivity of these variants. Four variants (Ile, Val, Ala and Leu) remained replication competent, whereas 3 others (Lys, Arg and Thr) showed impaired replication. 2 variants (Ile and Val) were showed to be resistant to lamivudine.
Hepatitis C virus (HCV)
Hepatitis C virus nonstructural region 5A (NS5A) protein, without its 146 amino-terminal amino acids fused to the DNA-binding domain of GAL4 strongly activates transcription in yeast and human hepatoma cells (Huh7). Transcriptional activation by HCV NS5A protein may play a role in viral replication and hepatocarcinogenesis.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Chuang WL: "Coinfction study of precore inutant and wild-type nepatitis B-like virus in duckliugs" Hepatology. 19. 569-576 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takano S: "Effects interfein β on non-A,non-B acute topatitis,Aplospective,randmized,controlled-dose study." Gastroenteiology. 107. 805-811 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsumura M: "Detection of α-fetoprotein in Rna,an indicator of remato genous spreading repotuullulas coninona in the circulation." Hepatology. 20. 1418-1425 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shiratori Y: "charcteristic difference of nepatocellular concinoma betueon nepotitis-B and -C nial infection in Japan." Hepatology. 22. 523-527 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shiratori Y: "Predictors of the efficaog of interferon thorapy in chronic nepatitis C virus infection." Gastroenterology. 113. 558-566 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato N: "Hepatitis C virus nonstructunal region 5A protein is a potent transcriptional activator." J Virology. 71. 8856-8859 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takano S,Omata M,Ohta M,Satomura Y.: "Prospective assessment of incidence of fulminant hepatitis in post-transfusion hepatitis : A study of 504 cases." Dig Dis Sci. 39. 28-32 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chuang WL,Omata M,Ehata T,Yokosuka O,Hosoda K,Imazeki F,Ohto M.: "Coinfection study of precore mutant and wild-type hepatitis B-like virus in duckling." Hepatology. 19. 569-576 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takano S,Ito Y,Yokosuka O,Ohto M,Uchiumi K,Hirota K,Omata M.: "A multicenter randomized controlled dose study of ursodeoxy cholic acid for chromic hepatitis C." Hepatology. 20. 558-564 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Omata M,Kato N.: "Recent advances in hepatitis C virus research." J Gastroenterology. 29. 377-382 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takano S,Satomura Y,Omata M: "Japan Acute Hepatitis Cooperative Study Group. Effects of interferon deta on non-A,non-B acute hepatitis : A prospective, randomized, controlled-dose study." Gastroenterology. 107. 805-811 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matumura M,Niwa Y,Kato N,Komatsu Y,Shiina S,Kawabe T,Kawase T,Toyoshima H,Ihori M,Shiratori Y,Omata M.: "Detection of alpha-fetoprotein mRNA,an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation : A possible predictor of metastatic hepatocellular carcinoma." Hepatology. 20. 1418-1425 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumura M,Niwa Y,Hikiba Y,Okano K,Kato N,Shiina S,Shiratori Y,Omata M.: "Sensitive assay for detection of hepatocellular carcinoma associated gene transcription (alpha-fetoprotein mRNA) in blood." Biochem Biophys Res Commun. 207. 813-818 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiratori Y,Shiina S,Imamura M,Kato N,Kanai F,Okudaira T,Teratani T,Tohgo G,Toda N,Ohashi M,Ogura K,Niwa Y,Kawabe T,Omata M.: "Characteristic difference of hepatocellular carcinoma between hepatitis-B and -C viral infection in Japan." Hepatology. 22. 1027-1033 (1995)

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

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] Tagawa M,Yokosuka O,Imazeki F,Ohto M,Omata M.: "Gene expression and active replication in the liver after injection of duck hepatitis B virus DNA into the peripheral vein of ducklings." J Hepatol. 24. 328-334 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ehata T,Yokosuka O,Imazeki F,Omata M.: "Point mutation in precore region of hepatitis B virus : Sequential changes from 'wild' to 'mutant'." J Gastroen Hepatol. 11. 566-574 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiratori Y,Kato N,Yokosuka O,Imazeki F,Hashimoto E,Hayashi N,Nakamura A,Asada M,Kuroda H,Tanaka N,Arakawa Y,Omata M.: "Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection." Gastroenterology. 113. 558-566 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiratori Y,Shiina S,Zhang PY,Ohno E,Okudaira T,Payawal DA,Ono-Nita SK,Imamura M,Kato N,Omata M.: "Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan?" Cancer. 80. 2060-2067 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato N,Lan KH,Ono-Nita SK,Shiratori Y,Omata M.: "Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator." J Virology. 71. 8856-8859 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shiratori Y,Kato N,Yokosuka O,Hashimoto E,Hayashi N,Nakamura A,Asada M,Kuroda H,Ohkubo H,Arakawa Y,Iwama A,Omata M.: "Quantitative assays for hepatitis C virus in serum as predictors of the long-term response to interferon." J Hepatol. 27. 437-444 (1997)

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

URL: 

Published: 1999-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi