Porcine reproductive and respiratory syndrome virus (PRRSV) induces IL-12p40 production through JNK-AP-1 and NF-κB signaling pathways

• PRRSV induces IL-12p40 production in vivo and in vitro.
• Porcine IL-12p40 promoter is isolated and characterized.
• PRRSV-induced IL-12p40 production depends on JNK-AP-1 and NF-κB signaling pathways.

Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects monocyte/macrophage cells and modulates cytokine production to regulate host immune response. IL-12p40 is the basic subunit of IL-12, a heterodimeric cytokine, which plays key roles in the cell-mediated immune response. In the present study, we demonstrated that PRRSV infection induced IL-12p40 production in vitro and in vivo. Subsequently, we showed that inhibitors of p38 MAPK, JNK, and NF-κB dramatically reduced PRRSV-induced IL-12p40 expression. To further characterize the molecular mechanism of IL-12p40 production induced by PRRSV infection, we cloned and analyzed the porcine IL-12p40 promoter, in which AP-1 and NF-κB motifs were found. In addition, both JNK-AP-1 and NF-κB signaling pathways were activated by PRRSV infection. Taken together, these data indicate that PRRSV induces IL-12p40 expression through the JNK-AP-1 and NF-κB signaling pathways. Our findings might facilitate our understanding of the molecular mechanisms of IL-12 production induced by PRRSV infection.