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Hepatitis C virus core protein down-regulates transcription of interferon-induced antiviral genes

Susana de Lucas1, Javier Bartolome, Vicente Carreno

  • 1Fundación para el Estudio de las Hepatitis Virales, Madrid 28015, Spain.

The Journal of Infectious Diseases
|December 14, 2004
PubMed
Abstract

Insights

Hepatitis C virus core protein inhibits interferon-alpha-induced antiviral gene expression by blocking ISGF3 binding to the ISRE. This study clarifies the role of HCV-Co in immune evasion.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Hepatitis C virus (HCV) proteins are known to interfere with the interferon-alpha (IFN-alpha)-induced Jak/STAT pathway.
  • The specific HCV protein responsible for this interference and its effect on IFN-induced gene expression remain debated.

Purpose of the Study:

  • To investigate the impact of the HCV core (HCV-Co) protein on the expression of IFN-induced antiviral genes.
  • To elucidate the mechanism by which HCV-Co influences the IFN signaling pathway.

Main Methods:

  • HepG2 cells were transfected with a plasmid encoding HCV-Co and treated with IFN-alpha.
  • mRNA levels of antiviral genes (MxA, PKR, 2'-5'OAS) were quantified.
  • Reporter gene assays (CAT analysis), electrophoretic mobility shift assays, and Western blot were employed to assess gene promoter activity and protein interactions.

Main Results:

  • HCV-Co expression led to a dose-dependent decrease in MxA mRNA levels, mediated by down-regulation of the MxA gene promoter.
  • HCV-Co protein was found to inhibit the binding of IFN-stimulated gene factor 3 (ISGF3) to the IFN-stimulated response element (ISRE).
  • The expression of other IFN-induced antiviral genes, PKR and 2'-5'OAS, was also down-regulated by HCV-Co.

Conclusions:

  • HCV-Co protein actively inhibits the transcription of IFN-alpha-induced antiviral genes.
  • This inhibition occurs through the suppression of ISGF3 binding to the ISRE, a critical step in the IFN signaling cascade.
  • The findings clarify the role of HCV-Co in viral immune evasion by disrupting the host's antiviral response.

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