FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1β Production

Foot-and-mouth disease virus (FMDV) infection causes inflammatory clinical symptoms, such as high fever and vesicular lesions, even death of animals. Interleukin-1 beta (IL-1 beta) is an inflammatory cytokine that plays an essential role in inflammatory responses against viral infection. The viruses have developed multiple strategies to induce the inflammatory responses, including regulation of IL-1 beta production. However, the molecular mechanism underlying the induction of IL-1 beta by FMDV remains not fully understood. Here, we found that FMDV robustly induced IL-1 beta production in macrophages and pigs. Infection of Casp-1 inhibitor-treated cells and NOD-, LRR- and pyrin domain-containing 3 (NLRP3)-knockdown cells indicated that NLRP3 is essential for FMDV-induced IL-1 beta secretion. More importantly, we found that FMDV L-pro associates with the NACHT and LRR domains of NLRP3 to promote NLRP3 inflammasome assembly and IL-1 beta secretion. Moreover, FMDV L-pro induces calcium influx and potassium efflux, which trigger NLRP3 activation. Our data revealed the mechanism underlying the activation of the NLRP3 inflammasome after FMDV L-pro expression, thus providing insights for the control of FMDV infection-induced inflammation.

Automated summary

Foot-and-mouth disease virus infection induces inflammatory responses, involving the production of interleukin-1 beta (IL-1 beta) and crucial involvement of NLRP3 in IL-1 beta secretion. Research demonstrates that FMDV L-pro interacts with NLRP3 to promote inflammasome assembly and IL-1 beta release, providing insights into controlling FMDV-induced inflammation.