Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling
Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling
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新加坡石斑鱼虹彩病毒是一种大型 DNA 病毒，通过细胞类型依赖性方式诱导非凋亡细胞死亡，并激发 ERK 信号传导
DOI：
10.1007/s10495-011-0616-y
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发表时间：
2011-08-01
期刊：
影响因子：
7.2
通讯作者：
Qin, Qiwei
中科院分区：
文献类型：
--
作者：
Huang, Xiaohong;Huang, Youhua;Qin, Qiwei
病毒诱导的细胞死亡，包括细胞凋亡和非凋亡细胞死亡，在病毒性疾病的发病机制中起着关键作用。新加坡石斑鱼虹膜病毒（SGIV）是ranusvirus属的一种新型虹膜病毒，在石斑鱼养殖业中造成高死亡率和严重的经济损失。通过荧光显微镜、电镜和生化分析，我们发现SGIV感染宿主（石斑鱼脾脏、EAGS）细胞引起非凋亡性程序性细胞死亡（PCD），其特征是细胞质空泡和内质网扩张，没有DNA片段化、凋亡小体和caspase激活。相比之下，SGIV在非宿主（fahead minnow， FHM）细胞中诱导了典型的凋亡，正如caspase激活和DNA断裂所证明的那样，这表明SGIV感染通过细胞类型依赖的方式诱导非凋亡细胞死亡。此外，病毒复制对SGIV诱导的非凋亡细胞死亡至关重要，而不是凋亡。值得注意的是，SGIV感染后，在EAGS细胞中未检测到线粒体跨膜电位的破坏（ΔΨm）和磷脂酰丝氨酸（PS）的外化，而在FHM细胞中检测到。此外，细胞外信号调节激酶（ERK）信号通路参与了SGIV感染诱导的非凋亡细胞死亡和病毒复制。这是DNA病毒介导的erk介导的非凋亡细胞死亡的首次证明。这些发现有助于理解虹膜病毒的发病机制。
Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genusRanavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication. This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to understanding the mechanisms of iridovirus pathogenesis.