1. Porcine reproductive and respiratory syndrome virus induces HMGB1 secretion via activating PKC-delta to trigger inflammatory response.
- Author
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Wang, Rong, Yang, Liping, Zhang, Yali, Li, Junyan, Xu, Liran, Xiao, Yueqiang, Zhang, Qian, Bai, Liang, Zhao, Sihai, Liu, Enqi, and Zhang, Yan-Jin
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PORCINE reproductive & respiratory syndrome , *HIGH mobility group proteins , *PROTEIN kinase C , *INFLAMMATION , *SMALL interfering RNA - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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