Hepatitis A virus protein 2B suppresses beta interferon (IFN) gene transcription by interfering with IFN regulatory factor 3 activation

J Gen Virol. 2008 Jul;89(Pt 7):1593-1604. doi: 10.1099/vir.0.83521-0.

Abstract

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of retinoic acid-inducible gene I-mediated and melanoma differentiation-associated gene 5-mediated beta interferon (IFN-beta) gene expression. This study showed that this is due to an interaction of HAV with mitochondrial antiviral signalling protein (MAVS)-dependent signalling, in which the viral non-structural protein 2B and the protein intermediate 3ABC recently suggested in this context seem to be involved, cooperatively affecting the activities of MAVS and the kinases TANK-binding kinase 1 (TBK1) and the inhibitor of NF-kappaB kinase epsilon (IKKepsilon). In consequence, interferon regulatory factor 3 (IRF-3) is not activated. As IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results in efficient suppression of IFN-beta synthesis. This ability might be of vital importance for HAV, which is an exceptionally slow growing virus sensitive to IFN-beta, as it allows the virus to establish infection and maintain virus replication for a longer period of time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Animals
  • Cell Line
  • Hepatitis A virus / physiology*
  • I-kappa B Kinase / antagonists & inhibitors
  • Interferon Regulatory Factor-3 / antagonists & inhibitors*
  • Interferon-beta / antagonists & inhibitors*
  • Macaca mulatta
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Transcription, Genetic
  • Viral Nonstructural Proteins / metabolism*

Substances

  • 2B protein, hepatitis A virus
  • 3ABC protein, virus
  • Adaptor Proteins, Signal Transducing
  • Interferon Regulatory Factor-3
  • Viral Nonstructural Proteins
  • Interferon-beta
  • Protein-Serine-Threonine Kinases
  • I-kappa B Kinase