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Hepatitis C virus core protein suppresses NF-kappaB activation and cyclooxygenase-2 expression by direct interaction

Myungsoo Joo1, Young S Hahn, Minjae Kwon

  • 1Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. myungsoo.joo@vanderbilt.edu

Journal of Virology
|May 28, 2005
PubMed

Insights

Hepatitis C virus (HCV) core protein disrupts immune cell function by inhibiting NF-kappaB activation and cyclooxygenase-2 (COX-2) expression in macrophages, potentially impacting HCV pathogenesis.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis C virus (HCV) infects hepatocytes and immune cells like macrophages.
  • The impact of HCV on macrophage function is not well understood.
  • Lipopolysaccharide (LPS) activates the IKK/NF-kappaB pathway, inducing cyclooxygenase-2 (COX-2) and prostaglandin production, key inflammatory mediators.

Purpose of the Study:

  • To investigate if HCV core protein interferes with IKK signalsome activity and COX-2 expression in activated macrophages.
  • To elucidate the molecular mechanisms by which HCV might modulate immune responses in macrophages.

Main Methods:

  • Reporter assays in RAW 264.7 and MH-S murine macrophage cell lines treated with LPS.
  • Analysis of IKK signalsome and IKKbeta kinase activities in HeLa and 293 cells.
  • Co-precipitation assays to assess interactions between HCV core and IKKbeta.
  • Western blotting to evaluate COX-2 expression levels.

Main Results:

  • HCV core inhibited NF-kappaB activation induced by LPS in macrophage cell lines.
  • HCV core suppressed IKK signalsome and IKKbeta kinase activities.
  • HCV core interacted with IKKbeta and prevented its nuclear translocation.
  • Ectopic expression of HCV core markedly suppressed LPS- or IKKbeta-induced COX-2 expression.

Conclusions:

  • HCV core protein suppresses IKK signalsome activity in macrophages.
  • This suppression leads to blunted COX-2 expression, potentially affecting inflammatory responses.
  • Further research is needed to determine the role of disrupted COX-2 expression in HCV pathogenesis.

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