Innate immune sensing of influenza A viral RNA through IFI16 promotes pyroptotic cell death

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, Ill 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.

Automated summary

The cytosolic DNA sensor IFI16 plays a crucial role in activating programmed cell death pathways in influenza A virus (IAV) infected cells by functioning as an RNA sensor for the virus. Its activation triggers the production of interferons and pro-inflammatory cytokines, promoting cell death and inflammatory responses.