Vitamin D deficiency may exacerbate or prolong arthritis in Chikungunya fever

Bhavana, Rao V. N.; Bhavana, Raman; Vatti, Narmada; Dirisana, Prabhakar Rao V.

doi:10.18203/2320-6012.ijrms20163300

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…Similarly, a weakened vitamin D pathway escalated hepatitis C virus infections and the incidence of hepatocellular carcinoma (Jin et al, 2018). Vitamin D deficiency prolonged inflammatory polyarthritis in Chikungunya virus (CHIKV)-infected individuals (Bhavana et al, 2016). On the other hand, dietary vitamin D supplementation significantly diminished influenza A virus replication and downregulated pro-inflammatory cytokines in the infected mice (Hayashi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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

Ratra

Kumar

Saha

et al. 2021

Preprint

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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-κB 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-κB 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-κB 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.

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Section: Introductionmentioning

confidence: 99%

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

Ratra

Kumar

Saha

et al. 2021

Preprint

View full text Add to dashboard Cite

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A Vitamin D–RelB/NF-κB Pathway Limits Chandipura Virus Multiplication by Rewiring the Homeostatic State of Autoregulatory Type 1 IFN–IRF7 Signaling

Ratra

Kumar

Saha

et al. 2022

The Journal of Immunology

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Besides its functions in the skeletomuscular system, vitamin D is known to alleviate viral-inflicted pathologies. However, the mechanism underlying protective vitamin D function remains unclear. We examined the role of vitamin D in controlling cellular infections by Chandipura virus, an RNA virus implicated in human epidemics. How immune signaling pathways, including those regulating NF-κB and IFN regulatory factors (IRFs), are activated in virus-infected cells has been well studied. Our investigation involving human- and mouse-derived cells revealed that vitamin D instructs the homeostatic state of these antiviral pathways, leading to cellular resilience to subsequent viral infections. In particular, vitamin D provoked autoregulatory type 1 IFN–IRF7 signaling even in the absence of virus infection by downmodulating the expression of the IFN-inhibitory NF-κB subunit RelB. Indeed, RelB deficiency rendered vitamin D treatment redundant, whereas IRF7 depletion abrogated antiviral vitamin D action. In sum, immune signaling homeostasis appears to connect micronutrients to antiviral immunity at the cellular level. The proposed link may have a bearing on shaping public health policy during an outbreak.

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Vitamin D deficiency may exacerbate or prolong arthritis in Chikungunya fever

Cited by 2 publications

References 7 publications

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

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

A Vitamin D–RelB/NF-κB Pathway Limits Chandipura Virus Multiplication by Rewiring the Homeostatic State of Autoregulatory Type 1 IFN–IRF7 Signaling

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