Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-beta induction by disrupting the VISA-associated complex

Cell Mol Immunol. 2010 Sep;7(5):341-8. doi: 10.1038/cmi.2010.36. Epub 2010 Aug 16.

Abstract

Viral RNAs produced during viral infection are recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). A central adapter protein downstream of RIG-I and MDA5 is the mitochondrial membrane protein virus-induced signaling adaptor (VISA), which mediates the induction of type I interferons (IFNs) through the activation of transcription factors such as nuclear factor-kappaB (NF-kappaB) and IFN-regulatory factor-3 (IRF3). Here we found that hepatitis B virus (HBV)-encoded X protein (HBx) acts as an inhibitor of virus-triggered IRF3 activation and IFN-beta induction. Reporter and plaque assays indicate that HBx inhibits signaling by components upstream but not downstream of VISA. Immunoprecipitation experiments indicate that HBx interacts with VISA and disrupts the association of VISA with its upstream and downstream components. These findings suggest that HBx acts as a suppressor of virus-triggered induction of type I IFNs, which explains the observation that HBV causes transient and chronic infection in hepatocytes but fails to activate the pattern recognition receptor-mediated IFN induction pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Line
  • Cricetinae
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / metabolism
  • Humans
  • Interferon Regulatory Factor-3 / immunology*
  • Interferon-beta / genetics
  • Interferon-beta / immunology*
  • Promoter Regions, Genetic
  • Protein Binding
  • Trans-Activators / immunology*
  • Trans-Activators / metabolism
  • Viral Regulatory and Accessory Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Interferon Regulatory Factor-3
  • MAVS protein, human
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • Interferon-beta