A Vitamin D–RelB/NF-κB Pathway Limits Chandipura Virus Multiplication by Rewiring the Homeostatic State of Autoregulatory Type 1 IFN–IRF7 Signaling
| Autor: | Yashika Ratra, Naveen Kumar, Manti K. Saha, Chandrima Bharadwaj, Chen Chongtham, Sachendra S. Bais, Guruprasad Medigeshi, Gopalakrishnan A. Arimbasseri, Soumen Basak |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 209:559-568 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|