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Cytotoxic T-lymphocytes inhibit hepatitis-B virus gene-expression by a noncytolytic mechanism in transgenic mice

Academic Article
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Overview

authors

  • Guidotti, Luca
  • Ando, K.
  • Hobbs, M. V.
  • Ishikawa, T.
  • Runkel, L.
  • Schreiber, R. D.
  • Chisari, Francis

publication date

  • 1994

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • During hepatitis B virus (HBV) infection, distinct host-virus interactions may establish the patterns of viral clearance and persistence and the extent of virus-associated pathology. It is generally thought that HBV-specific class I-restricted cytotoxic T lymphocytes (CTLs) play a critical role in this process by destroying infected hepatocytes. This cytopathic mechanism, however, could be lethal if most of the hepatocytes are infected. In the current study, we demonstrate that class I-restricted HBV-specific CTLs profoundly suppress hepatocellular HBV gene expression in HBV transgenic mice by a noncytolytic process, the strength of which greatly exceeds the cytopathic effect of the CTLs in magnitude and duration. We also show that the regulatory effect of the CTLs is initially mediated by interferon gamma and tumor necrosis factor alpha, is delayed in onset, and becomes independent of these cytokines shortly after it begins. The data indicate that the anti-viral CTL response activates a complex regulatory cascade that inhibits hepatocellular HBV gene expression without killing the cell. The extent to which this mechanism contributes to viral clearance or viral persistence during HBV infection remains to be determined.

subject areas

  • Animals
  • Cytokines
  • Cytotoxicity, Immunologic
  • Gene Expression Regulation, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B virus
  • Interferon-gamma
  • Liver Diseases
  • Mice
  • Mice, Transgenic
  • RNA, Messenger
  • RNA, Viral
  • T-Lymphocytes, Cytotoxic
  • Tumor Necrosis Factor-alpha
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Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.91.9.3764

PubMed ID

  • 8170985
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Additional Document Info

start page

  • 3764

end page

  • 3768

volume

  • 91

issue

  • 9

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