Hepatitis C virus RNA replication is resistant to tumour necrosis factor-alpha

J Gen Virol. 2003 May;84(Pt 5):1253-1259. doi: 10.1099/vir.0.18997-0.


It was demonstrated using self-replicating hepatitis C virus (HCV) RNAs that both types of interferons (IFNs) (in particular IFN-alpha and IFN-gamma) are potent inhibitors of HCV replication in Huh-7 cells. Because IFN-gamma and tumour necrosis factor (TNF)-alpha trigger a partially overlapping set of antiviral defence mechanisms, it is tempting to speculate that TNF-alpha also inhibits HCV replication. However, this study shows that TNF-alpha does not affect HCV protein and RNA synthesis, nor does it synergistically enhance the inhibitory effect of IFN-gamma. Taken together, these results demonstrate that HCV replication in Huh-7 cells is highly resistant to TNF-alpha. It is, therefore, unlikely that the increased production of TNF-alpha, which is seen in many hepatitis C patients, contributes to HCV clearance by inducing antiviral defence mechanisms in infected hepatocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Drug Resistance, Viral
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity*
  • Hepacivirus / physiology
  • Humans
  • Interferon-gamma / pharmacology
  • RNA, Viral / biosynthesis*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Virus Replication / drug effects*


  • Antiviral Agents
  • RNA, Viral
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma