FCV activates NLRP3 inflammasome through ion-dependent pathway to promote IL-1β secretion.

Feline calicivirus (FCV) poses a significant threat to the health of susceptible animals in the global epidemic. The inflammasome plays a crucial role in the inflammatory process induced by pathogens, functioning in resisting their invasion, responding to cellular damage, and maintaining internal environmental homeostasis.FCV infection in cats causes inflammation,and the regulatory mecha-nisms of the NLRP3 inflammasome on inflammatory factors in infected cells urgently require further investigation.This study focuses on this inflammasome as the entry point, focusing on its activation signal that activates IL-1β secretion.Through cellular experiments, it analyzes the molecular mechanisms and logical relationships between this inflammasome, intracellular environ-ment, pyroptosis, the regulation of IL-1β secretion by viral-encoded proteins.The results showed that FCV-infected cells induced the activation and assembly of the NLRP3 inflammasome, thereby activating this signaling. FCV-induced IL-1β secretion was dependent on the activation of this inflammasome. In the early stages of infection, the activation of this inflammasome and IL-1β secretion were dependent on cellular Ca influx and K efflux. IL-1β secretion also relied on FCV-induced pyroptosis;The activation of this inflammasome by the FCV-encoded protein p32/LC and the subsequent induction of IL-1β secretion are contingent upon the function of its in mediating cellular Ca influx and K efflux.In summary, this study demonstrates that following FCV infection of cells, its p32 and LC proteins activate the NLRP3 inflammasome activation signal in a manner dependent on Ca influx and K efflux,Induce IL-1β secretion. In addition, FCV-induced pyroptosis also triggers the secretion of IL-1β. The findings of this study elucidate the leading to inflammatory mechanisms of FCV from a novel perspective, providing new drug targets for the design and screening of anti-inflammatory drugs.