Citation

  • Authors: Fensterl, V., Grotheer, D., Berk, I., Schlemminger, S., Vallbracht, A., Dotzauer, A.
  • Year: 2005
  • Journal: J Virol 79 10968-77
  • Applications: in vitro / DNA / jetPEI
  • Cell types:
    1. Name: FRhK-4
    2. Name: MRC-5
      Description: Human lung fibroblast cells
      Known as: MRC5, MRC 5

Abstract

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of double-stranded RNA (dsRNA)-induced beta interferon (IFN-beta) gene expression. In this report, we show that this is due to an interaction of HAV with the intracellular dsRNA-induced retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway upstream of the kinases responsible for interferon regulatory factor 3 (IRF-3) phosphorylation (TBK1 and IKKepsilon). In consequence, IRF-3 is not activated for nuclear translocation and gene induction. In addition, we found that HAV reduces TRIF (TIR domain-containing adaptor inducing IFN-beta)-mediated IRF-3 activation, which is part of the Toll-like receptor 3 signaling pathway. As IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results in efficient suppression of IFN-beta synthesis. This ability of HAV seems to be of considerable importance for HAV replication, as HAV is not resistant to IFN-beta, and it may allow the virus to establish infection and preserve the sites of virus production in later stages of the infection.

Pubmed