Nuclear Factor κB2 p52 Protein Has a Role in Antiviral Immunity through IκB Kinase ϵ-dependent Induction of Sp1 Protein and Interleukin 15

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. Background: IKKϵ can promote the ability of p52 to transactivate gene expression in a manner requiring p65. Results: p52 is induced by TLR3 activation and regulates Sp1 transcription. Sp1 promotes the transcription of IL-15. Both events require the presence of IKKϵ and p52. Conclusion: p52 is a target for IKKϵ in antiviral immunity. Significance: This study reports a role for NFκB2 in the induction of antiviral gene expression.