Open AccessDistinct Roles for the NF-κB RelA Subunit during Antiviral Innate Immune Responses
Author(s) -
Suresh H. Basagoudanavar,
Roshan J. Thapa,
Shoko Nogusa,
Junmei Wang,
Amer A. Beg,
Siddharth Balachandran
Publication year - 2011
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02213-10
Subject(s) - biology , innate immune system , interferon , autocrine signalling , immune system , virus , transcription factor , virology , interferon type i , immunology , microbiology and biotechnology , gene , cell culture , genetics
Production of type I interferons (IFNs; prominently, IFN-α/β) following virus infection is a pivotal antiviral innate immune response in higher vertebrates. The synthesis of IFN-β proceeds via the virus-induced assembly of the transcription factors IRF-3/7, ATF-2/c-Jun, and NF-κB on theifn β promoter. Surprisingly, recent data indicate that the NF-κB subunit RelA is not essential for virus-stimulatedifn β expression. Here, we show that RelA instead sustains autocrine IFN-β signaling prior to infection. In the absence of RelA, virus infection results in significantly delayedifn β induction and consequently defective secondary antiviral gene expression. While RelA is not required forifn β expression after infection, it is nonetheless essential for fully one-fourth of double-stranded RNA (dsRNA)-activated genes, including several mediators of inflammation and immune cell recruitment. Further, RelA directly regulates a small subset of interferon-stimulated genes (ISGs). Finally, RelA also protects cells from dsRNA-triggered RIP1-dependent programmed necrosis. Taken together, our findings suggest distinct roles for RelA in antiviral innate immunity: RelA maintains autocrine IFN-β signaling in uninfected cells, facilitates inflammatory and adaptive immune responses following infection, and promotes infected-cell survival during this process.