Biology subjects

Bais, S. S.

Publications and source records attributed to Bais, S. S..

3 recordsLinked to original sources

bioRxiv2025

A dominant role of cell death in limiting Chandipura virus propagation at cell-saturating high multiplicity of infection

Viruses transit from a low to high multiplicity of infection (MOI) regime in infected tissues. Type-1 interferons (IFNs) enforce a cellular state refractory to virus multiplication, while the death of infected cells eliminates viral replicative niche. Here, we investigated how these two innate antiviral mechanisms cooperate at various MOIs upon cell infection by Chandipura virus (CHPV), a cytopathic RNA virus implicated in several outbreaks of acute encephalitis in India. We found that as expected, a gradual increase in the input MOI from 0.02 to 2 led to a proportionate surge in the viral yield. Surprisingly, a further rise to MOI 20 caused a reduction in the progeny titer. Our mathematical modeling together with ex vivo infection studies involving mutant cells suggested that cell death - more so than virus-induced type-1 IFNs - restricted CHPV propagation at cell-saturating high MOIs, leading to a net fall in the yield at MOI 20. We argue that the distinct involvement of innate immune pathways at varied MOIs imparts robust cellular defense against cytopathic viruses. Significance sentenceCell death - more so than type-1 interferons - limits Chandipura virus propagation at cell-saturating high multiplicity of infection. Highlights# Type-1 IFNs and cell death cooperate at varied MOI in limiting CHPV multiplication. # At sub-saturating low MOI, type-1 IFNs play a dominant role in controlling CHPV propagation. # At cell-saturating high MOI, cell death determines the progeny yield.

systems biology↗

bioRxiv2021

A vitamin D-RelB/NF-κB pathway limits Chandipura virus multiplication by rewiring the homeostatic state of autoregulatory type 1 interferon-IRF7 signaling

Besides its functions in the skeletomuscular system, vitamin D also promotes protective immunity against viral pathogens. Viral sensing by mammalian cells triggers nuclear activation of RelA/NF-{kappa}B and IRF3 factors, which collaborate in mediating the early induction of antiviral type 1 interferons (T1-IFNs). Autocrine T1-IFN signaling further accumulates otherwise negligibly expressed IRF7 in virus-infected cells that then sustains T1-IFN production in a positive feedback. Surprisingly, prior cell-culture studies revealed that vitamin D actually suppresses signal-induced RelA activation. Indeed, it remains unclear how vitamin D limits viral multiplication in a cell-autonomous manner. Here, we examined the role of vitamin D in controlling cellular infections by the Chandipura virus (CHPV), a cytoplasmic RNA virus implicated in human epidemics. We found that vitamin D conditioning produced an altered cell state less permissive for CHPV multiplication because of the heightened expression of T1-IFNs. It is thought that viruses also induce a distinct RelB/NF-{kappa}B activity, which counteracts RelA-driven T1-IFN expressions in infected cells. Our analyses instead characterized a basal nuclear RelB activity, which was downregulated upon vitamin D-mediated suppression of RelB synthesis. Interestingly, this vitamin D-RelB pathway provoked IRF7-mediated positive autoregulation augmenting constitutive T1-IFN expressions even in the absence of viral infections. Accordingly, RelB deficiency rendered redundant, while IRF7 depletion abrogated antiviral vitamin D actions. In sum, our study suggests that the homeostatic state of the signaling circuitry comprising of the NF-{kappa}B and T1-IFN pathways connects micronutrients to antiviral immunity at the cellular level. Significance statementVitamin D limits viral infections, but the underlying mechanism remains unclear. Linking micronutrients to antiviral immunity, Ratra et al. characterize an immune signaling circuitry engaged by vitamin D that generates a cellular state less permissive to infections by Chandipura virus, a pathogen of public health importance.

immunology↗

bioRxiv2019

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

In response to infection by RNA viruses, mammalian cells typically activate RelA-containing NF-{kappa}B heterodimers, which induce genes encoding interferon-{beta} 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-{kappa}B linked to its pro-survival properties.\n\nHighlightsO_LILack of RelA NF-{kappa}B leads to reduced growth of CHPV ex vivo\nC_LIO_LIRelA deficiency exacerbates cell-death processes upon CHPV infection\nC_LIO_LIInhibition of cell-death processes restores CHPV multiplication in RelA-deficient MEFs\nC_LI

immunology↗