Open AccessThe adaptor protein FHL2 enhances the cellular innate immune response to influenza A virus infection
Author(s) -
Nordhoff Carolin,
Hillesheim Andrea,
Walter Beate M.,
Haasbach Emanuel,
Planz Oliver,
Ehrhardt Christina,
Ludwig Stephan,
Wixler Viktor
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01787.x
Subject(s) - biology , innate immune system , interferon , signal transducing adaptor protein , microbiology and biotechnology , transcription factor , influenza a virus , virus , virology , immune system , interferon type i , signal transduction , gene , immunology , genetics
Summary The innate immune response of influenza A virus‐infected cells is predominantly mediated by type I interferon‐induced proteins. Expression of the interferon β (IFNβ) itself is initiated by accumulating viral RNA and is transmitted by different signalling cascades that feed into activation of the three transcriptional elements located in the IFNβ promoter, AP‐1, IRF‐3 and NF‐κB. FHL2 (four‐and‐a‐half LIM domain protein 2) is an adaptor molecule that shuttles between membrane and nucleus regulating signalling cascades and gene transcription. Here we describe FHL2 as a novel regulator of influenza A virus propagation. Using mouse FHL2 wild‐type, knockout and rescued cells and human epithelial cells with different expression levels of FHL2 we showed that FHL2 decreases influenza A virus propagation by regulating the intrinsic cellular antiviral immune response. On virus infection FHL2 translocates into the nucleus, potentiating the IRF‐3‐dependent transcription of the IFNβ gene.