ABSTRACT Coronaviruses (CoVs) are a family of RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans. Here, we use porcine epidemic diarrhea virus (PEDV) as a model of CoVs to illustrate the reciprocal regulation between CoV infection and pyroptosis. For the first time, we elucidate the molecular mechanism of porcine gasdermin D (pGSDMD)-mediated pyroptosis and demonstrate that amino acids R238, T239, and F240 within pGSDMD-p30 are critical for pyroptosis. Furthermore, 3C-like protease Nsp5 from SARS-CoV-2, MERS-CoV, PDCoV, and PEDV can cleave pGSDMD at the Q193-G194 junction to produce two fragments unable to trigger pyroptosis. The two cleaved fragments could not inhibit PEDV replication. In addition, Nsp5 from SARS-CoV-2 and MERS-CoV also cleave human GSDMD (hGSDMD). Therefore, we provide clear evidence that PEDV may utilize the Nsp5-GSDMD pathway to inhibit pyroptosis and, thus, facilitate viral replication during the initial period, suggesting an important strategy for the coronaviruses to sustain their infection.
【저자키워드】 coronavirus, pyroptosis, nsp5, GSDMD, 【초록키워드】 SARS-CoV-2, coronavirus, Infection, protease, molecular mechanism, virus, MERS-CoV, Replication, viral replication, humans, pathway, CoV, RNA virus, Critical, Amino acid, Evidence, epidemic diarrhea, gasdermin D, Regulation, CoVs, CoV infection, PEDV, hepatic disease, initial, addition, inhibit, facilitate, cleaved, cleave, 【제목키워드】 fragment,