Resveratrol alleviated inflammatory responses induced by cytopathic bovine viral diarrhea virus infection via NLRP3 inflammasome induced pyroptosis.

Bovine viral diarrhea virus (BVDV) infection causes diarrhea and inflammation in cattle and other animals. Vaccines usually provide limited protection against it due to the emergence of mutant strains. Therefore, developing novel strategies of defense against BVDV infection is urgently needed. Resveratrol (RES) is a natural polyphenol widely found in plants and has anti-inflammatory and antiviral effects. RES was used to pretreat bovine BT and PBMC cells before BVDV infection to explore whether it has an anti-BVDV effect. Mechanistically, pre-treatment with RES inhibited the expression of the NLRP3 inflammasome by inhibiting activation of NF-κB signalling pathway and the activation of NLRP3 inflammasome through K+ channel and ROS pathway, thereby inhibiting the production of IL-1β and IL-18. Furthermore, RES alleviated the inflammatory response induced by BVDV by inhibiting the expression and activation of Gasdermin D (GSDMD), and further inhibiting the secretion of IL-1β and IL-18. Moreover, it may interact with the NLRP3 inflammasome or the GSDMD protein to inhibit pyroptosis. Additionally, RES can inhibit the replication of BVDV, thereby alleviating any injuries caused by it. In conclusion, this study confirmed that RES can inhibit the expression of the NLRP3 inflammasome and GSDMD, thereby inhibiting the pyroptosis and inflammatory response induced by BVDV infection. The results provide a basis for screening natural drugs with the function of preventing BVDV.