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Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures

Academic Article
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Overview

authors

  • Pasquetto, V.
  • Wieland, Stefan
  • Uprichard, S. L.
  • Tripodi, M.
  • Chisari, Francis

publication date

  • June 2002

journal

  • Journal of Virology  Journal

abstract

  • We have previously shown that alpha/beta interferon (IFN-alpha/beta) and gamma interferon (IFN-gamma) inhibit hepatitis B virus (HBV) replication by eliminating pregenomic RNA containing viral capsids from the hepatocyte. We have also shown that HBV-specific cytotoxic T lymphocytes that induce IFN-gamma and tumor necrosis factor alpha (TNF-alpha) in the liver can inhibit HBV gene expression by destabilizing preformed viral mRNA. In order to further study the antiviral activity of IFN-alpha/beta, IFN-gamma, and TNF-alpha at the molecular level, we sought to reproduce these observations in an in vitro system. Accordingly, hepatocytes were derived from the livers of HBV-transgenic mice that also expressed the constitutively active cytoplasmic domain of the human hepatocyte growth factor receptor (c-Met). Here, we show that the resultant well-differentiated, continuous hepatocyte cell lines (HBV-Met) replicate HBV and that viral replication in these cells is efficiently controlled by IFN-alpha/beta or IFN-gamma, which eliminate pregenomic RNA-containing capsids from the cells as they do in the liver. Furthermore, we demonstrate that IFN-gamma, but not IFN-alpha/beta, is capable of inhibiting HBV gene expression in this system, especially when it acts synergistically with TNF-alpha. These cells should facilitate the analysis of the intracellular signaling pathways and effector mechanisms responsible for these antiviral effects.

subject areas

  • Animals
  • Antiviral Agents
  • Capsid
  • Cells, Cultured
  • Cytoplasm
  • DNA Replication
  • DNA, Viral
  • Hepatitis B virus
  • Hepatocytes
  • Humans
  • Interferon-beta
  • Interferon-gamma
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-met
  • RNA, Viral
  • Tumor Necrosis Factor-alpha
  • Virus Replication
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Identity

PubMed Central ID

  • PMC137053

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.76.11.5646-5653.2002

PubMed ID

  • 11991993
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Additional Document Info

start page

  • 5646

end page

  • 5653

volume

  • 76

issue

  • 11

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