Foot-and-Mouth Disease Virus Induces Porcine Gasdermin E-Mediated Pyroptosis through the Protease Activity of 3C^pro.

ABSTRACT: Foot-and-mouth disease (FMD) is an acute, highly contagious disease of cloven-hoofed animals caused by FMD virus (FMDV). Currently, the molecular pathogenesis of FMDV infection remains poorly understood. Here, we demonstrated that FMDV infection induced gasdermin E (GSDME)-mediated pyroptosis independent of caspase-3 activity. Further studies showed that FMDV 3C^pro cleaved porcine GSDME (pGSDME) at the Q271-G272 junction adjacent to the cleavage site (D268-A269) of porcine caspase-3 (pCASP3). The inhibition of enzyme activity of 3C^pro failed to cleave pGSDME and induce pyroptosis. Furthermore, overexpression of pCASP3 or 3C^pro-mediated cleavage fragment pGSDME-NT was sufficient to induce pyroptosis. Moreover, the knockdown of GSDME attenuated the pyroptosis

SUBMITTER: Ren X 

PROVIDER: S-EPMC10373541 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature