Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33

J Gen Virol. 2012 Jan;93(Pt 1):83-92. doi: 10.1099/vir.0.033860-0. Epub 2011 Sep 28.


Viperin is a type-I and -II interferon-inducible intracytoplasmic protein that mediates antiviral activity against several viruses. A previous study has reported that viperin could limit hepatitis C virus (HCV) replication in vitro. However, the underlying mechanism remains elusive. In the present study, we found that overexpression of viperin could inhibit HCV replication in a dose-dependent manner in both the replicon and HCVcc systems. Furthermore, through co-immunoprecipitation and laser confocal microscopic analysis, viperin was found to interact with the host protein hVAP-33. Mutagenesis analysis demonstrated that the anti-HCV activity of viperin was located to its C terminus, which was required for the interaction with the C-terminal domain of hVAP-33. Competitive co-immunoprecipitation analysis showed that viperin could interact competitively with hVAP-33, and could therefore interfere with its interactions with HCV NS5A. In summary, these findings suggest a novel mechanism by which viperin inhibits HCV replication, possibly through binding to host protein hVAP-33 and interfering with its interaction with NS5A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Down-Regulation*
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatitis C / genetics
  • Hepatitis C / metabolism*
  • Hepatitis C / virology
  • Humans
  • Oxidoreductases Acting on CH-CH Group Donors
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*


  • Proteins
  • VAPA protein, human
  • Vesicular Transport Proteins
  • Viral Nonstructural Proteins
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human
  • NS-5 protein, hepatitis C virus