PRRSV infection inhibits CSFV C-strain replication via GSDMD-mediated pyroptosis

Classical swine fever virus (CSFV) and porcine productive and respiratory syndrome virus (PRRSV) both are significant infectious pathogens in pigs and pose great threats to the healthy development of the pig industry. PRRSV infection often reduces the antibody level of the CSFV attenuated vaccine and even leads to immune failure. In order to elucidate the potential mechanism of CSFV proliferation inhibition by PRRSV and screen out drugs that enhance the vaccine immune effect, we conducted experiments in the PAM39 cell line that can simultaneously support both PRRSV and CSFV infection. The results showed that PRRSV infection could induce gasdermin D (GSDMD) cleavage, promote cell pyroptosis, increase IL-1β secretion, and then inhibit CSFV replication. However, Astragalus polysaccharide treatment could reverse this phenomenon. The results elucidate the molecular mechanism of CSFV vaccine immune failure caused by PRRSV co-infection from the perspective of pyroptosis and provide a scientific basis for the prevention and control of clinical co-infection diseases.