Cytopathic and noncytopathic interferon responses in cells expressing hepatitis C virus subgenomic replicons

J Virol. 2003 Oct;77(20):10769-79. doi: 10.1128/jvi.77.20.10769-10779.2003.


Hepatitis C virus (HCV) is the only known positive-stranded RNA virus that causes persistent lifelong infections in humans. Accumulation of HCV RNA can be inhibited with alpha interferon (IFN-alpha) in vivo and in culture cells. We used cell-based assay systems to investigate the mechanisms responsible for the cytokine-induced inhibition of HCV replication. The results showed that IFN-alpha could suppress the accumulation of viral RNA by a noncytopathic pathway and could also induce apoptosis of virally infected cells in a concentration- and cell line-dependent fashion. Whereas the noncytopathic IFN-alpha response depended on a functional Jak-STAT signal transduction pathway, it did not appear to require double-stranded RNA-dependent pathways. Moreover, we found that functional proteasomes were required for establishment of the IFN-alpha response against HCV. Based on the results described in this study we propose a model for the mechanism by which IFN-alpha therapy suppresses HCV replication in chronic infections by both cytopathic and noncytopathic means.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • DNA-Binding Proteins / physiology
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Humans
  • Interferon-alpha / pharmacology*
  • Interferon-beta / biosynthesis
  • RNA, Viral / analysis
  • RNA, Viral / physiology
  • Receptors, Virus / drug effects
  • Replicon*
  • STAT2 Transcription Factor
  • Signal Transduction
  • Trans-Activators / physiology


  • Antiviral Agents
  • DNA-Binding Proteins
  • Interferon-alpha
  • RNA, Viral
  • Receptors, Virus
  • STAT2 Transcription Factor
  • Trans-Activators
  • Interferon-beta