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 (PKCδ). HMGB1 secretion was positively correlated with PKCδ activation in PRRSV-infected cells in a dose and time-dependent manner. Suppression of PKCδ with inhibitor and siRNA significantly blocked PRRSV-induced HMGB1 translocation and secretion, which indicates PKCδ activation is essential for the PRRSV-mediated HMGB1 secretion. In addition, PKCδ knockdown in PRRSV-infected cells led to downregulation of inflammatory cytokines, including IL-1beta and IL-6. Moreover, PRRSV E and pORF5a proteins were found to activate PKCδ and consequent HMGB1 secretion. These results demonstrate PRRSV activates PKCδ to induce HMGB1 secretion via E and pORF5a. This finding provides insights on the inflammatory response and pathogenesis of PRRSV infection.

猪繁殖与呼吸综合症病毒（PRRSV）在受感染的猪中引起炎症性损伤。PRRSV诱导高流动性第1号框（HMGB1）的分泌，增强炎症反应。但是，PRRSV诱导HMGB1分泌的机制尚不清楚。在这里，我们发现PRRSV通过激活蛋白激酶C-δ（PKCδ）诱导HMGB1分泌。HMGB1分泌与PRRSV感染的细胞中PKCδ激活呈正相关，呈剂量和时间依赖性。用抑制剂和siRNA抑制PKCδ可显着阻断PRRSV诱导的HMGB1移位和分泌，这表明PKCδ激活对于PRRSV介导的HMGB1分泌至关重要。此外，PRRSV感染细胞中的PKCδ敲低导致包括IL-1beta和IL-6在内的炎性细胞因子的下调。而且，发现PRRSV E和pORF5a蛋白可激活PKCδ和随后的HMGB1分泌。这些结果表明，PRRSV通过E和pORF5a激活PKCδ诱导HMGB1分泌。这一发现为PRRSV感染的炎症反应和发病机理提供了见解。