Stress-activated protein kinases are involved in porcine reproductive and respiratory syndrome virus infection and modulate virus-induced cytokine production

The present study examined the role of the p38 MAPK and JNK pathways during PRRSV infection in immortalized porcine alveolar macrophage (PAM) cells. Infection with PRRSV was found to progressively activate p38 and JNK1/2 up to 36 h postinfection and then their phosphorylation levels dramatically decreased to baseline at 48 h postinfection. In contrast, UV-inactivated PRRSV failed to trigger phosphorylation of these SAPKs, indicating that the post-entry process is responsible for their activation. Independent treatment of cells with a selective p38 or JNK inhibitor markedly impaired PRRSV infection, resulting in significant reduction in synthesis of viral genomic and subgenomic RNAs, viral protein expression, and progeny virus production. Notably, cytokine production in PAM cells infected with PRRSV was shown to be altered by inhibiting these SAPKs. Altogether, our data suggest that the p38 and JNK signaling pathways play pivotal roles in PRRSV replication and may regulate immune responses during virus infection.

► PRRSV infection activated the p38 and JNK1/2 pathways in immortalized PAM cells.
► UV-inactivated virus failed to induce p38 and JNK1/2 activation.
► Inhibition of p38 or JNK activation markedly suppressed PRRSV replication.
► SAPK inhibitors altered expression of immune-response genes in PRRSV-infected cells.