NLRP3 inflammasome in major swine viral infections: Host defense and viral antagonism

The NLRP3 inflammasome is a cytosolic signaling platform that drives caspase-1-dependent maturation of IL-1β and IL-18 and gasdermin D (GSDMD)-mediated pyroptosis. During infection with major porcine viruses - including African swine fever virus, porcine reproductive and respiratory syndrome virus, pseudorabies virus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, and porcine circovirus type 2, NLRP3 exerts opposing effects: moderate activation restricts viral propagation, whereas sustained stimulation drives tissue injury. We review how structurally unrelated viral proteins converge on limited upstream events - endolysosomal damage, ion flux, mitochondrial injury, ER stress, and the ubiquitin-autophagy network. Because genetically distinct porcine pathogens exploit this same regulatory axis, it represents a shared point of vulnerability. We assess therapeutic options targeting NLRP3 assembly, GSDMD pore formation, and host proteostasis, and highlight questions requiring validation in porcine cells and pigs.