title: The adaptor protein FHL2 enhances the cellular innate immune response to influenza A virus infection.
abstract: 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.
authors.affiliation: Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Nordhoff
authors.forename: Andrea
authors.initials: A
authors.lastname: Hillesheim
authors.forename: Beate M
authors.initials: BM
authors.lastname: Walter
authors.forename: Emanuel
authors.initials: E
authors.lastname: Haasbach
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Viktor
authors.initials: V
authors.lastname: Wixler
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C105987:FHL2 protein, human; C491382:Fhl2 protein, mouse; D050838:Interferon Regulatory Factor-3; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors