Hepatitis A virus protein 2B suppresses beta interferon (IFN) gene transcription by interfering with IFN regulatory factor 3 activation.
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-beta) 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-kappaB kinase epsilon (IKKepsilon). In consequence, interferon regulatory factor 3 (IRF-3) is not activated. As IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results in efficient suppression of IFN-beta synthesis. This ability might be of vital importance for HAV, which is an exceptionally slow growing virus sensitive to IFN-beta, as it allows the virus to establish infection and maintain virus replication for a longer period of time.
Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
Dajana
D
Paulmann
Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
Thomas
T
Magulski
Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
Rebecca
R
Schwarz
Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
Lisa
L
Heitmann
Children's Hospital, Department 1, University of Tübingen, Silcherstraße 7, D-72076 Tübingen, Germany.
Bertram
B
Flehmig
Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
Angelika
A
Vallbracht
Department of Virology, University of Bremen, Leobener Straße/UFT, D-28359 Bremen, Germany.
Andreas
A
Dotzauer
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors; D000818:Animals; D002460:Cell Line; D030041:Hepatitis A virus / Q000502:physiology*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors*; D016899:Interferon-beta / Q000037:antagonists & inhibitors*; D008253:Macaca mulatta; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
C116507:2B protein, hepatitis A virus; C109754:3ABC protein, virus; D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase