biostudies-literatureZheng WNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)Leading innovative and Entrepreneur Team Introduction Program of Zhejiang79https://www.ebi.ac.uk/biostudies/studies/S-EPMC9950063biostudies-literatureUnknown8(1)Innate immunity represents one of the main host responses to viral infection.^1-3 STING (Stimulator of interferon genes), a crucial immune adapter functioning in host cells, mediates cGAS (Cyclic GMP-AMP Synthase) sensing of exogenous and endogenous DNA fragments and generates innate immune responses.⁴ Whether STING activation was involved in infection and replication of enterovirus remains largely unknown. In the present study, we discovered that human enterovirus A71 (EV-A71) infection triggered STING activation in a cGAS dependent manner. EV-A71 infection caused mitochondrial damage and the discharge of mitochondrial DNA into the cytosol of infected cells. However, during EV-A71 infection, cGAS-STING activation was attenuated. EV-A71 proteins were screened and the vSignal transduction and targeted therapyTRAF3 activates STING-mediated suppression of EV-A71 and target of viral evasion.PMC99500639216920381701988821722398210238431970151320410068177216931900133Liu XRui YYe RGuo FYu XFSu JZheng WLou MZhou ZXia FfalseTRAF3 activates STING-mediated suppression of EV-A71 and target of viral evasion.Innate immunity represents one of the main host responses to viral infection.^1-3 STING (Stimulator of interferon genes), a crucial immune adapter functioning in host cells, mediates cGAS (Cyclic GMP-AMP Synthase) sensing of exogenous and endogenous DNA fragments and generates innate immune responses.⁴ Whether STING activation was involved in infection and replication of enterovirus remains largely unknown. In the present study, we discovered that human enterovirus A71 (EV-A71) infection triggered STING activation in a cGAS dependent manner. EV-A71 infection caused mitochondrial damage and the discharge of mitochondrial DNA into the cytosol of infected cells. However, during EV-A71 infection, cGAS-STING activation was attenuated. EV-A71 proteins were screened and the v2023-01-01T00:00:00Z2023 Feb2025-04-26T13:48:46.529Z2025-04-06T14:19:19.889ZS-EPMC99500633682314710.1038/s41392-022-01287-2