Lack of a role of the interferon-stimulated response element-like region in interferon alpha -induced suppression of Hepatitis B virus in vitro.
The antiviral effect of interferon-alpha (IFNalpha) on hepatitis B virus (HBV) is well documented in vitro and in vivo, but the mechanisms involved are elusive. Recently, an interferon-stimulated response like element (ISRE) competent for binding of interferon-stimulated gene factor-3gamma (p48) has been identified in the HBV enhancer I region. Mutation of this element was shown to abrogate IFNalpha-mediated reduction of HBV X-gene promoter-driven reporter gene expression. This suggested a role of the ISRE and of p48 in IFNalpha-induced antiviral activity against productive HBV infection. Here, we analyzed the antiviral effect of both IFNalpha and enhanced p48 expression on complete HBV genomes containing the wild-type or mutated ISRE. In human hepatoma cells transfected with both genomes, viral RNA and replicative intermediates were reduced by IFNalpha treatment to a similar degree. Enhanced p48 expression increased IFNalpha-induced suppression of HBV RNA significantly from 75 +/- 22.5% to 46 +/- 9.8%, but this was independent of the integrity of the ISRE-like region. These data imply that p48 neither mediates the antiviral activity of IFNalpha against HBV nor down-regulates enhancer I activity by binding directly to the HBV ISRE-like region, but rather argue for an indirect role of p48.
Rang
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Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistrabetae 52, D-20251 Hamburg, Germany.
Heise
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Will
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D000998:Antiviral Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D012367:RNA, Viral; D014157:Transcription Factors