The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2.
The p7 protein of the hepatitis C virus induces cell death differently from the influenza A virus viroporin M2.
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DOI：
10.1016/j.virusres.2012.12.005
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发表时间：
2013-03
期刊：
影响因子：
5
通讯作者：
Tan YJ
中科院分区：
文献类型：
--
作者：
Aweya JJ;Mak TM;Lim SG;Tan YJ
HCV p7蛋白过表达诱导Huh 7.5细胞凋亡。BMP 7诱导的细胞凋亡涉及内在和外在途径。BMP 7诱导的细胞凋亡不依赖于其离子通道活性。HSP 7在功能上与甲型流感病毒的充分表征的M2蛋白相似，但它们在自噬细胞死亡的激活方面不同。大多数病毒编码调节宿主细胞死亡信号的蛋白质。对于丙型肝炎病毒（HCV）感染，已经在体外和体内观察到细胞凋亡和其他形式的细胞死亡，但对这种复杂的病毒-宿主相互作用的详细理解尚不清楚。本研究检测了HCV p7蛋白在诱导细胞死亡中所起的作用。通过测量凋亡的两个标志，caspase-3/7激活和内源性PARP的切割，显示p7蛋白的过表达诱导Huh7.5细胞中的凋亡。此外，p7诱导的细胞凋亡是半胱天冬酶依赖性的，涉及内在和外在途径。与甲型流感病毒的M2蛋白类似，p7诱导的细胞凋亡不依赖于其离子通道活性。免疫共沉淀实验进一步表明，M2和p7都与必不可少的自噬蛋白Beclin-1相互作用。然而，只有M2蛋白可以引起LC 3-II水平的增加，LC 3-II是自噬活性的指标。因此，尽管p7蛋白在功能上与充分表征的M2蛋白相似，但它们在自噬细胞死亡的激活方面不同。两者合计，这些结果揭示了更多的HCV p7离子通道蛋白和宿主细胞中的细胞死亡诱导之间的关系。
► Overexpression of HCV p7 protein induces apoptosis in Huh7.5 cells. ► p7-induced apoptosis involves both the intrinsic and extrinsic pathways. ► p7-induced apoptosis is independent of its ion channel activity. ► p7 is functionally similar to the well-characterized M2 protein of influenza A virus but they differ in their activation of autophagic cell-death. Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined the role played by the HCV p7 protein in the induction of cell-death. By measuring caspase-3/7 activation and cleavage of endogenous PARP, two hallmarks of apoptosis, the overexpression of p7 protein was shown to induce apoptosis in Huh7.5 cells. Furthermore, p7-induced apoptosis is caspase-dependent and involves both the intrinsic and extrinsic pathways. Similar to the M2 protein of influenza A virus, p7-induced apoptosis is independent of its ion channel activity. Coimmunoprecipitation experiments further showed that both M2 and p7 interact with the essential autophagy protein Beclin-1. However, only the M2 protein could cause an increase in the level of LC3-II, which is an indicator of autophagic activity. Thus, although the p7 protein is functionally similar to the well-characterized M2 protein, they differ in their activation of autophagic cell-death. Taken together, these results shed more light on the relationship between the HCV p7 ion channel protein and cell-death induction in host cells.
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影响因子：
4.8
作者：
Garcia-Calvo, M;Peterson, EP;Thornberry, NA
通讯作者：
Thornberry, NA
DOI：
10.3390/v3081342
发表时间：
2011-08
期刊：
Viruses
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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