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Interferon-regulated pathways that control hepatitis B virus replication in transgenic mice

Academic Article
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Overview

authors

  • Guidotti, Luca
  • Morris, A.
  • Mendez, H.
  • Koch, R.
  • Silverman, R. H.
  • Williams, B. R. G.
  • Chisari, Francis

publication date

  • March 2002

journal

  • Journal of Virology  Journal

abstract

  • We previously showed that the intrahepatic induction of cytokines such as alpha/beta interferon (IFN-alpha/beta) and gamma interferon (IFN-gamma) inhibits hepatitis B virus (HBV) replication noncytopathically in the livers of transgenic mice. The intracellular pathway(s) responsible for this effect is still poorly understood. To identify interferon (IFN)-inducible intracellular genes that could play a role in our system, we crossed HBV transgenic mice with mice deficient in IFN regulatory factor 1 (IRF-1), the double-stranded RNA-activated protein kinase (PKR), or RNase L (RNase L) (IRF-1(-/-), PKR(-/-), or RNase L(-/-) mice, respectively), three well-characterized IFN-inducible genes that mediate antiviral activity. We showed that unmanipulated IRF-1(-/-) or PKR(-/-) transgenic mice replicate HBV in the liver at slightly higher levels than the respective controls, suggesting that both IRF-1 and PKR individually appear to mediate signals that modulate HBV replication under basal conditions. These same animals were responsive to the antiviral effects of the IFN-alpha/beta inducer poly(I-C) or recombinant murine IFN-gamma, suggesting that under these conditions, either the IRF-1 or the PKR genes can mediate the antiviral activity of the IFNs or other IFN-inducible genes mediate the antiviral effects. Finally, RNase L(-/-) transgenic mice were undistinguishable from controls under basal conditions and after poly(I-C) or IFN-gamma administration, suggesting that RNase L does not modulate HBV replication in this model.

subject areas

  • Animals
  • DNA-Binding Proteins
  • Endoribonucleases
  • Gene Expression Regulation, Viral
  • Hepatitis B
  • Hepatitis B virus
  • Interferon Regulatory Factor-1
  • Interferon-gamma
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphoproteins
  • Poly I-C
  • Recombinant Proteins
  • Virus Replication
  • eIF-2 Kinase
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Identity

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.76.6.2617-2621.2002

PubMed ID

  • 11861827
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Additional Document Info

start page

  • 2617

end page

  • 2621

volume

  • 76

issue

  • 6

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