Classic swine fever virus NS2 protein leads to the induction of cell cycle arrest at S-phase and endoplasmic reticulum stress.
Classic swine fever virus NS2 protein leads to the induction of cell cycle arrest at S-phase and endoplasmic reticulum stress.
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经典猪瘟病毒 NS2 蛋白导致细胞周期停滞在 S 期和内质网应激
DOI：
10.1186/1743-422x-7-4
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发表时间：
2010-01-11
期刊：
影响因子：
4.8
通讯作者：
Dai C
中科院分区：
文献类型：
--
作者：
Tang QH;Zhang YM;Fan L;Tong G;He L;Dai C
【摘要】：背景猪瘟(CSF)是由猪瘟病毒(CSFV)强毒株引起的猪的一种出血性疾病,以弥散性血管内凝血、血小板减少和免疫抑制为特征,猪内皮血管细胞是猪瘟病毒的靶细胞之一。在本报告中，我们通过检测CSFV NS2蛋白对细胞生长和细胞周期进展的影响，研究了以前未知的CSFV NS2蛋白的亚细胞定位和功能。结果建立了表达CSFV NS2的稳定猪脐静脉内皮细胞系（SUVEC），并显示该蛋白定位于内质网（ER）。细胞分析表明，由于细胞周期停滞在 S 期，表达 NS2 的细胞系的复制受到 20-30% 的抑制。 NS2 蛋白还诱导 ER 应激并激活核转录因子 kappa B (NF-κB)。在表达 NS2 的细胞中观察到细胞周期蛋白 A 转录水平显着增加，但同时伴随着细胞周期蛋白 A 蛋白的蛋白酶体降解的增加。因此，CSFV NS2蛋白诱导细胞周期阻滞在S期与细胞周期蛋白A蛋白周转增加有关，而不是细胞周期蛋白A转录下调。结论所有数据都表明，CSFV NS2蛋白通过诱导S期阻滞来调节细胞生长和细胞周期进展，并提供有利于病毒复制的细胞环境。这些发现提供了有关尚未充分表征的猪瘟病毒 NS2 蛋白功能的新信息。
BackgroundClassical swine fever (CSF) caused by virulent strains of Classical swine fever virus (CSFV) is a haemorrhagic disease of pigs, characterized by disseminated intravascular coagulation, thrombocytopoenia and immunosuppression, and the swine endothelial vascular cell is one of the CSFV target cells. In this report, we investigated the previously unknown subcellular localization and function of CSFV NS2 protein by examining its effects on cell growth and cell cycle progression.ResultsStable swine umbilical vein endothelial cell line (SUVEC) expressing CSFV NS2 were established and showed that the protein localized to the endoplasmic reticulum (ER). Cellular analysis revealed that replication of NS2-expressing cell lines was inhibited by 20-30% due to cell cycle arrest at S-phase. The NS2 protein also induced ER stress and activated the nuclear transcription factor kappa B (NF-κB). A significant increase in cyclin A transcriptional levels was observed in NS2-expressing cells but was accompanied by a concomitant increase in the proteasomal degradation of cyclin A protein. Therefore, the induction of cell cycle arrest at S-phase by CSFV NS2 protein is associated with increased turnover of cyclin A protein rather than the down-regulation of cyclin A transcription.ConclusionsAll the data suggest that CSFV NS2 protein modulate the cellular growth and cell cycle progression through inducing the S-phase arrest and provide a cellular environment that is advantageous for viral replication. These findings provide novel information on the function of the poorly characterized CSFV NS2 protein.