Porcine reproductive and respiratory syndrome virus (PRRSV) up-regulates IL-15 through PKCβ1-TAK1-NF-κB signaling pathway

- PRRSV infection can induce IL-15 expression in lungs of pigs.
- The conventional PKC, PKCβ1, plays a critical role in PRRSV-induced IL-15 production.
- PRRSV up-regulates IL-15 through MAVS/TRIF-PKCβ1-TAK1-NF-κB signaling pathways.

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is one of the most important infectious diseases in swine industry. IL-15 is a pleiotropic cytokine and has been shown to be essential to transform NKs, CD8 T cells, and other cells of the immune systems into functional effectors. Here, we demonstrated that the broad-spectrum or conventional PKC inhibitors repressed PRRSV-induced IL-15 expression and NF-κB activation. Subsequently, we found that the PKCβ specific inhibitor inhibited PRRSV-induced IL-15 production, which was also confirmed by knock-down of PKCβ1, suggesting that PKCβ1 is involved in the PRRSV-induced IL-15 expression. In addition, we demonstrated that PRRSV activated NF-κB through PKCβ1-induced TAK1 activation. Finally, we demonstrated that PRRSV activated PKCβ1 dependent on the participation of TRIF and MAVS. These data indicate that PRRSV up-regulates IL-15 through TRIF/MAVS-PKCβ1-TAK1-NF-κB signaling pathway. These findings will provide new insights into the molecular mechanisms of IL-15 production induced by PRRSV.