Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon.


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.


Citations per Year

101 Citations

Semantic Scholar estimates that this publication has 101 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Fensterl2005HepatitisAV, title={Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon.}, author={Volker Fensterl and Dajana Grotheer and I. G. Berk and Stefanie Schlemminger and Angelika Vallbracht and Andreas Dotzauer}, journal={Journal of virology}, year={2005}, volume={79 17}, pages={10968-77} }