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著者: Volker Fensterl, Dajana Grotheer, Iris Berk, Stefanie Schlemminger, Angelika Vallbracht, Andreas Dotzauer
雑誌名: J Virol. 2005 Sep;79(17):10968-77. doi: 10.1128/JVI.79.17.10968-10977.2005.
Abstract/Text
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.
PMID 16103148 J Virol. 2005 Sep;79(17):10968-77. doi: 10.1128/JVI.79.17.10968-10977.2005.
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