Porcine reproductive and respiratory syndrome virus induces HMGB1 secretion via activating PKC-delta to trigger inflammatory response

Porcine reproductive and respiratory syndrome virus (PRRSV) causes inflammatory injuries in infected pigs. PRRSV induces secretion of high mobility group box 1 (HMGB1) that enhances inflammatory response. However, the mechanism of PRRSV-induced HMGB1 secretion is unknown. Here, we discovered PRRSV induced HMGB1 secretion via activating protein kinase C-delta (PKC delta). HMGB1 secretion was positively correlated with PKC delta activation in PRRSV-infected cells in a dose and time-dependent manner. Suppression of PKC delta with inhibitor and siRNA significantly blocked PRRSV-induced HMGB1 translocation and secretion, which indicates PKC delta activation is essential for the PRRSV-mediated HMGB1 secretion. In addition, PKC delta knockdown in PRRSV-infected cells led to downregulation of inflammatory cytokines, including IL-lbeta and IL-6. Moreover, PRRSV E and pORF5a proteins were found to activate PKC delta and consequent HMGB1 secretion. These results demonstrate PRRSV activates PKC delta to induce HMGB1 secretion via E and pORF5a. This finding provides insights on the inflammatory response and pathogenesis of PRRSV infection.