TY - JOUR T1 - Coronaviruses using different strategies to antagonize antiviral responses and pyroptosis JF - bioRxiv DO - 10.1101/2022.07.29.502014 SP - 2022.07.29.502014 AU - Xinyu Fu AU - Yang Yang AU - Weilv Xu AU - Danyue Li AU - Xinyue Li AU - Nan Chen AU - Qian Lv AU - Yuhua Shi AU - Xiaoliang Li AU - Jidong Xu AU - Fushan Shi Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/08/02/2022.07.29.502014.abstract N2 - Viral infection triggers inflammasome-mediated caspase-1 activation. However, less is known about how viruses use the active caspase-1 to evade host immune response. Here, we use porcine epidemic diarrhea virus (PEDV) as a model of coronaviruses (CoVs) to illustrate the sophisticated regulation of CoVs to counteract IFN-I signaling and pyroptosis. We show that PEDV infection stabilizes caspase-1 expression via papain-like protease PLP2’s deubiquitinase activity and the enhanced stabilization of caspase-1 disrupts IFN-I signaling by cleaving RIG-I at D189 residue. Meanwhile, PLP2 can degrade GSDMD-p30 by removing its K27-linked ubiquitin chain at K275 to restrain pyroptosis. Papain-like proteases from other genera of CoVs (PDCoV and SARS-CoV-2) have the similar activity to degrade GSDMD-p30. We further demonstrate that SARS-CoV-2 N protein induced NLRP3 inflammasome activation also uses the active caspase-1 to counter IFN-I signaling by cleaving RIG-I. Therefore, our work unravels a novel antagonistic mechanism employed by CoVs to evade host antiviral response.Competing Interest StatementThe authors have declared no competing interest. ER -