title: Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase epsilon-dependent induction of Sp1 protein and interleukin 15.
abstract: In this study we describe a previously unreported function for NFκB2, an NFκB family transcription factor, in antiviral immunity. NFκB2 is induced in response to poly(I:C), a mimic of viral dsRNA. Poly(I:C), acting via TLR3, induces p52-dependent transactivation of a reporter gene in a manner that requires the kinase activity of IκB kinase ε (IKKε) and the transactivating potential of RelA/p65. We identify a novel NFκB2 binding site in the promoter of the transcription factor Sp1 that is required for Sp1 gene transcription activated by poly(I:C). We show that Sp1 is required for IL-15 induction by both poly(I:C) and respiratory syncytial virus, a response that also requires NFκB2 and IKKε. Our study identifies NFκB2 as a target for IKKε in antiviral immunity and describes, for the first time, a role for NFκB2 in the regulation of gene expression in response to viral infection.
authors.affiliation: From the Immunology Research Centre, Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland,. Electronic address: Sarah.Doyle@tcd.ie.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Doyle
authors.affiliation: the Department of Microbiology and Immunology, University of Maryland, Baltimore, School of Medicine, Baltimore, Maryland 21201.
authors.forename: Kari Ann
authors.initials: KA
authors.lastname: Shirey
authors.affiliation: From the Immunology Research Centre, Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Anne F
authors.initials: AF
authors.lastname: McGettrick
authors.affiliation: From the Immunology Research Centre, Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Kenny
authors.affiliation: From the Immunology Research Centre, Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: the Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Caffrey
authors.affiliation: the Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland, and.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Gargan
authors.affiliation: From the Immunology Research Centre, Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Quinn
authors.affiliation: the Institute for BioMedical Research-Medical Research Council (IBR-MRC) Centre for Immune Regulation, College of Medicine and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Caamaño
authors.affiliation: the Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland, and.
authors.forename: Paul
authors.initials: P
authors.lastname: Moynagh
authors.affiliation: the Department of Microbiology and Immunology, University of Maryland, Baltimore, School of Medicine, Baltimore, Maryland 21201.
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Vogel
authors.affiliation: From the Immunology Research Centre, Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Luke A
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007369:Interferon Inducers / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics / Q000276:immunology; D016329:Sp1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C569274:IL15 protein, human; D007369:Interferon Inducers; D019409:Interleukin-15; D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; C498207:Nfkb2 protein, mouse; C498143:RELA protein, human; C498144:Rela protein, mouse; D016329:Sp1 Transcription Factor; C495344:TLR3 protein, human; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; D011070:Poly I-C
keywords: Cytokine Induction; Gene Regulation; Innate Immunity; Molecular Biology; NF-κB; Signal Transduction; Sp1; Toll-like Receptor (TLR); Transcription; Viral Immunology