Porcine epidemic diarrhea virus nucleoprotein contributes to HMGB1 transcription and release by interacting with C/EBP-β.

Porcine epidemic diarrhea virus nucleoprotein contributes to HMGB1 transcription and release by interacting with C/EBP-β.
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猪流行性腹泻病毒核蛋白通过与 C/EBP-β 相互作用促进 HMGB1 转录和释放

DOI:
10.18632/oncotarget.11991
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发表时间:
2016-11-15
期刊:
影响因子:
--
通讯作者:
Mao X
Mao X
中科院分区:
其他
文献类型:
--
作者:
Huan CC;Wang HX;Sheng XX;Wang R;Wang X;Liao Y;Liu QF;Tong GZ;Ding C;Fan HJ;Wu JQ;Mao X

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猪流行性腹泻是由猪流行性腹泻病毒(PEDV)感染引起的一种严重的猪肠道传染病。我们的研究表明,PEDV感染导致了促炎细胞因子的上调。同时,PEDV感染和病毒核蛋白的过度表达在体外导致高迁移率族蛋白1的乙酰化和释放,这是一种重要的促炎反应介质,参与了各种炎症性疾病的发病。我们的研究还表明,SIRT1、组蛋白乙酰转移酶和NF-κB调节HMGB1的乙酰化和释放。染色质免疫沉淀、双荧光素酶报告基因检测和免疫共沉淀实验表明,PEDV-N通过与C/EBP-β相互作用而诱导HMGB1转录,并与HMGB1启动子区域的C/EBP基序结合。总之,我们的数据表明,在PEDV感染过程中,PEDV-N参与了HMGB1的转录和随后的HMGB1的释放/乙酰化。
Porcine epidemic diarrhea is a devastating swine enteric disease, which is caused by porcine epidemic diarrhea virus (PEDV) infection. Our studies demonstrated that PEDV infection resulted in the up-regulation of proinflammatory cytokines. Meanwhile, PEDV infection and overexpression of viral nucleoprotein resulted in the acetylation and release of high mobility group box 1 proteins in vitro, an important proinflammatory response mediator, which contributes to the pathogenesis of various inflammatory diseases. Our studies also showed that SIRT1, histone acetyltransferase, and NF-κB regulated the acetylation and release of HMGB1. Chromatin immunoprecipitation, dual-luciferase reporter gene assay, and co-immunoprecipitation experiments illustrated that PEDV-N could induce HMGB1 transcription by interacting with C/EBP-β, which could bind to C/EBP motif in HMGB1 promotor region. Collectively, our data indicate PEDV-N contributes to HMGB1 transcription and the subsequent release/acetylation of HMGB1 during PEDV infection.