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

• Published in: Virology (New York, N.Y.) N.Y.), 2018-05, Vol.518, p.172-183
• Main Authors: Wang, Rong, Yang, Liping, Zhang, Yali, Li, Junyan, Xu, Liran, Xiao, Yueqiang, Zhang, Qian, Bai, Liang, Zhao, Sihai, Liu, Enqi, Zhang, Yan-Jin
• Format: Article
• Language: English
• Subjects: High-mobility group box 1 (HMGB1); Inflammatory response; PKC-delta; Porcine reproductive and respiratory syndrome virus (PRRSV); Protein kinase C (PKC); PRRSV E and ORF5a
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2018.02.021

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. •PRRSV induces HMGB1 translocation and secretion via PKCδ activation.•PKCδ knockdown in PRRSV-infected cells leads to reduction of inflammatory cytokines.•PRRSV E and pORF5a proteins are responsible for HMGB1 secretion via activating PKCδ.•E and pORF5a induce HMGB1 secretion and consequently activate inflammatory response.