tetano
Editor, Senior Moderator
iScience
. 2021 Dec 31;25(1):103714.
doi: 10.1016/j.isci.2021.103714. eCollection 2022 Jan 21.
Innate immune sensing of influenza A viral RNA through IFI16 promotes pyroptotic cell death
Shalabh Mishra[SUP] 1 [/SUP], Athira S Raj[SUP] 1 [/SUP], Akhilesh Kumar[SUP] 1 [/SUP], Ashwathi Rajeevan[SUP] 1 [/SUP], Puja Kumari[SUP] 1 [/SUP], Himanshu Kumar[SUP] 1 2 [/SUP]
Affiliations
Abstract
Programmed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus (IAV) infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for the influenza A virus by interacting with genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). On the contrary, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. Collectively, these results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.
Keywords: Biological sciences; Immunology; Virology.
. 2021 Dec 31;25(1):103714.
doi: 10.1016/j.isci.2021.103714. eCollection 2022 Jan 21.
Innate immune sensing of influenza A viral RNA through IFI16 promotes pyroptotic cell death
Shalabh Mishra[SUP] 1 [/SUP], Athira S Raj[SUP] 1 [/SUP], Akhilesh Kumar[SUP] 1 [/SUP], Ashwathi Rajeevan[SUP] 1 [/SUP], Puja Kumari[SUP] 1 [/SUP], Himanshu Kumar[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35072006
- PMCID: PMC8762390
- DOI: 10.1016/j.isci.2021.103714
Abstract
Programmed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus (IAV) infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for the influenza A virus by interacting with genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). On the contrary, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. Collectively, these results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.
Keywords: Biological sciences; Immunology; Virology.