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.
Original language | English |
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Pages (from-to) | 25066-25075 |
Number of pages | 10 |
Journal | The Journal of biological chemistry |
Volume | 288 |
Issue number | 35 |
DOIs | |
Publication status | Published - 30 Aug 2013 |
Keywords
- Animals
- Gene Expression Regulation/drug effects
- HEK293 Cells
- Humans
- I-kappa B Kinase/genetics
- Interferon Inducers/pharmacology
- Interleukin-15/genetics
- Mice
- Mice, Knockout
- NF-kappa B p52 Subunit/genetics
- Poly I-C/pharmacology
- Respiratory Syncytial Virus Infections/genetics
- Respiratory Syncytial Viruses/genetics
- Response Elements/genetics
- Sp1 Transcription Factor/biosynthesis
- Toll-Like Receptor 3/genetics
- Transcription Factor RelA/genetics