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

被引：18

作者：

Wang, Rong ^{[1
]}

Yang, Liping ^{[2
]}

Zhang, Yali ^{[1
]}

Li, Junyan ^{[1
]}

Xu, Liran ^{[1
]}

Xiao, Yueqiang ^{[3
]}

Zhang, Qian ^{[3
]}

Bai, Liang ^{[1
]}

Zhao, Sihai ^{[1
]}

Liu, Enqi ^{[1
]}

Zhang, Yan-Jin ^{[2
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Med, Lab Anim Ctr, Xian, Shaanxi, Peoples R China

[2] Univ Maryland, VA MD Coll Vet Med, Mol Virol Lab, College Pk, MD 20742 USA

[3] Shandong Binzhou Anim Sci & Vet Med Acad, Binzhou, Shandong, Peoples R China

来源：

VIROLOGY | 2018年 / 518卷

基金：

中国国家自然科学基金;

关键词：

Porcine reproductive and respiratory syndrome virus (PRRSV); High-mobility group box 1 (HMGB1); Protein kinase C (PKC); PKC-delta; Inflammatory response; PRRSV E and ORF5a; PROTEIN-KINASE-C; MOBILITY GROUP BOX-1; NUCLEAR TRANSLOCATION; SIGNAL-TRANSDUCTION; GNOTOBIOTIC PIGS; GENE-EXPRESSION; ORF5A PROTEIN; INFECTION; REPLICATION; TRANSCRIPTION;

D O I：

10.1016/j.virol.2018.02.021

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：172 / 183

页数：12

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