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

1 Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany 2 Children's Hospital, Department 1, University of Tübingen, Silcherstraße 7, D-72076 Tübingen, Germany Correspondence Andreas Dotzauer dotzauer{at}uni-bremen.de 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- β ) 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 (IKK ). In consequence, interferon regulatory factor 3 (IRF-3) is not activated. As IRF-3 is necessary for IFN- β transcription, inhibition of this factor results in efficient suppression of IFN- β synthesis. This ability might be of vital importance for HAV, which is an exceptionally slow growing virus sensitive to IFN- β , as it allows the virus to establish infection and maintain virus replication for a longer period of time. These authors contributed equally to this work.