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

Porcine reproductive and respiratory syndrome virus induces HMGB1 secretion via activating PKC-delta to trigger inflammatory response. Virology. 2018 Mar 06;518:172-183 Authors: Wang R, Yang L, Zhang Y, Li J, Xu L, Xiao Y, Zhang Q, Bai L, Zhao S, Liu E, Zhang YJ Abstract 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. PMID: 29522984 [PubMed - as supplied by publisher]
Source: Virology - Category: Virology Authors: Tags: Virology Source Type: research