Chandipura virus requires pro-survival RelA NF-κB function for its propagation

Abstract

In response to infection by RNA viruses, mammalian cells typically activate RelA-containing NF-κB heterodimers, which induce genes encoding interferon-β and other antiviral mediators. Therefore, RelA is commonly thought to function as an anti-viral transcription factor. Notably, virus-specific mechanisms often modify mainstay immune pathways. Despite its human health relevance, how Chandipura virus (CHPV) per se interacts with the cellular signaling machinery has not been investigated. Here, we report that RelA deficiency abrogated antiviral gene expressions and yet surprisingly caused diminished growth of CHPV in mouse embryonic fibroblasts. Our experimental studies clarified that RelA-dependent synthesis of pro-survival factors restrained infection-inflicted cell death, and that exacerbated cell death processes prevented multiplication of CHPV in RelA-deficient cells. In sum, we identify a pro-viral function of the immune-activating transcription factor RelA NF-κB linked to its pro-survival properties. Highlights Lack of RelA NF-κB leads to reduced growth of CHPV ex vivo RelA deficiency exacerbates cell-death processes upon CHPV infection Inhibition of cell-death processes restores CHPV multiplication in RelA-deficient MEFs