1887

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-) 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-B kinase ϵ (IKKϵ). In consequence, interferon regulatory factor 3 (IRF-3) is not activated. As IRF-3 is necessary for IFN- transcription, inhibition of this factor results in efficient suppression of IFN- synthesis. This ability might be of vital importance for HAV, which is an exceptionally slow growing virus sensitive to IFN-, as it allows the virus to establish infection and maintain virus replication for a longer period of time.

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2008-07-01
2021-01-27
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