PRRSV inhibited the proliferation of CSFV by inducing IL-1 beta maturation via NLRP3 inflammasome activation

PRRSV and CSFV are both common infectious pathogens in porcine populations, posing significant threats to the healthy development of the porcine industry. Vaccine immunization is the main way to prevent and control these two diseases. Increasing studies have demonstrated that there is an interaction between PRRSV co-infection and CSFV vaccine immune failure. To investigate the effect of PRRSV infection on CSFV proliferation and its molecular mechanism, the proliferation dynamics of PRRSV/CSFV, the NLRP3 inflammasome components, and IL1 beta expression levels were detected in PRRSV/CSFV alone- or co-infection. Subsequently, the relationship between inflammasome activation, IL-1 beta expression, and CSFV proliferation was analyzed through the construction of an inflammasome activation model, specific siRNA interference, and specific inhibitor treatment. The results showed that CSFV infection had a poor regulatory effect on NLRP3 inflammasome activation and IL-1 beta maturation, but PRRSV and CSFV co-infection could significantly up-regulate the expression of NLRP3 and ASC, induce Caspase-1 activation, and promote IL-1 beta maturation. It was further determined that NLRP3 inflammasome components played important roles in IL-1 beta maturation and inhibiting CSFV proliferation by PRRSV. Additional experiments indicated that PRRSV replication is essential for NLRP3 inflammasome activation, IL-1 beta maturation, and CSFV proliferation inhibition. More importantly, NLRP3 inflammasome activation is regulated by the TLR4-MyD88-NF-kappa B pathways. In conclusion, PRRSV infection induced IL-1 beta maturation by activating the NLRP3 inflammasome through the TLR4-MyD88-NF-kappa B pathways and then inhibited the proliferation of CSFV. These data further improved the theoretical basis for PRRSV inducing inflammatory factors and leading to the failure of CSFV immunization.

Automated summary

PRRSV and CSFV are common infectious pathogens in pig populations, posing significant threats to the healthy development of the pig industry. Vaccine immunization is the main method to prevent and control these two diseases. Studies have shown that PRRSV co-infection affects the immune response to CSFV vaccine. In this study, it was found that PRRSV and CSFV co-infection significantly increased the expression of NLRP3 and ASC, activated Caspase-1, and promoted IL-1 beta maturation, leading to the inhibition of CSFV proliferation. It was also determined that the activation of NLRP3 inflammasome is regulated by the TLR4-MyD88-NF-kappa B pathways.