biostudies-literatureLuo Jiangsu agricultural science and technology independent innovation fund projectational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaBeijing Natural Science Foundation740-756https://www.ebi.ac.uk/biostudies/studies/S-EPMC9067533biostudies-literatureUnknown13(1)African swine fever virus (ASFV), a large and complex cytoplasmic double-stranded DNA virus, has developed multiple strategies to evade the antiviral innate immune responses. Cytosolic DNA arising from invading ASFV is mainly detected by the cyclic GMP-AMP synthase (cGAS) and then triggers a series of innate immune responses to prevent virus invasion. However, the immune escape mechanism of ASFV remains to be fully clarified. The pS273R of ASFV is a member of the SUMO-1-specific protease family and is crucial for valid virus replication. In this study, we identified pS273R as a suppressor of cGAS-STING pathway mediated type I interferon (IFN) production by ASFV genomic open reading frame screening. The pS273R was further confirmed as an inhibitor of IFN production as well as its downstreamVirulenceThe African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKε.PMC906753332172867; 318724502021YFD18001006202002CX(21)2035Ni JChen NChen QZhang JGuo YJiang SZhu HChen HMeurens FZheng WZhang QZhu JLuo JXia NShao QCao QfalseThe African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKε.African swine fever virus (ASFV), a large and complex cytoplasmic double-stranded DNA virus, has developed multiple strategies to evade the antiviral innate immune responses. Cytosolic DNA arising from invading ASFV is mainly detected by the cyclic GMP-AMP synthase (cGAS) and then triggers a series of innate immune responses to prevent virus invasion. However, the immune escape mechanism of ASFV remains to be fully clarified. The pS273R of ASFV is a member of the SUMO-1-specific protease family and is crucial for valid virus replication. In this study, we identified pS273R as a suppressor of cGAS-STING pathway mediated type I interferon (IFN) production by ASFV genomic open reading frame screening. The pS273R was further confirmed as an inhibitor of IFN production as well as its downstream2022-01-01T00:00:00Z2022 Dec2026-04-08T17:27:10.863Z2025-04-04T10:02:02.122ZS-EPMC90675333543710410.1080/21505594.2022.2065962