The underlying mechanism of Porcine Teschovirus 2 3Cpro antagonizing the NLRP3 inflammasome.

Porcine teschovirus (PTV) can cause diseases such as poliomyelitis, pneumonia, and reproductive disorders in sows, but research on the pathogenesis of PTV infection is limited. In this investigation, we observed that PTV infection inhibits the activation of the NLRP3 inflammasome. PTV 3Cpro inhibits the activation of the NLRP3 inflammasome and pyroptosis by degrading NLRP3, IL-1β, and GSDMD. The degradation mechanism of 3Cpro involves the interaction of NLRP3, IL-1β, and 3Cpro, and 3Cpro degrades IL-1β through the caspase pathway. The mechanism by which PTV 3Cpro degrades GSDMD diverges from other picornavirus, remaining mechanistically elusive. Moreover, 3Cpro cannot degrade target proteins after their protease activity is lost. Our study provides new insights into the mechanism of antagonizing programmed cell death by PTV.