Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase epsilon-dependent induction of Sp1 protein and interleukin 15

J Biol Chem. 2013 Aug 30;288(35):25066-25075. doi: 10.1074/jbc.M113.469122. Epub 2013 Jul 19.

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.

Keywords: Cytokine Induction; Gene Regulation; Innate Immunity; Molecular Biology; NF-κB; Signal Transduction; Sp1; Toll-like Receptor (TLR); Transcription; Viral Immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / immunology*
  • I-kappa B Kinase / metabolism
  • Interferon Inducers / pharmacology
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Mice
  • Mice, Knockout
  • NF-kappa B p52 Subunit / genetics
  • NF-kappa B p52 Subunit / immunology*
  • NF-kappa B p52 Subunit / metabolism
  • Poly I-C / pharmacology
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / metabolism
  • Response Elements / genetics
  • Response Elements / immunology
  • Sp1 Transcription Factor / biosynthesis
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / immunology*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 3 / metabolism
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / immunology
  • Transcription Factor RelA / metabolism

Substances

  • IL15 protein, human
  • Interferon Inducers
  • Interleukin-15
  • NF-kappa B p52 Subunit
  • NFKB2 protein, human
  • Nfkb2 protein, mouse
  • RELA protein, human
  • Rela protein, mouse
  • Sp1 Transcription Factor
  • TLR3 protein, human
  • TLR3 protein, mouse
  • Toll-Like Receptor 3
  • Transcription Factor RelA
  • I-kappa B Kinase
  • Poly I-C