Japanese encephalitis virus counteracts BST2 restriction via its envelope protein E
Japanese encephalitis virus counteracts BST2 restriction via its envelope protein E
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日本脑炎病毒通过其包膜蛋白 E 抵消 BST2 限制
DOI：
10.1016/j.viro1.2017.07.008
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Liu Yalan
中科院分区：
文献类型：
--
作者：
Li Mei;Wang Ping;Zheng Zifeng;Hu Kai;Zhang Mudan;Guan Xinmeng;Fu Ming;Zhang Di;Wang Wei;Xiao Gengfu;Hu Qinxue;Liu Yalan
已有文献证明BST2通过将新产生的病毒粒子交联到细胞膜上来限制包膜病毒的释放。然而，目前尚不清楚BST2是否以及如何抑制通过分泌途径发芽的包膜病毒的释放。在这里，我们证明BST2限制日本脑炎病毒（JEV）的释放，其出芽发生在er -高尔基体中间室，反过来，JEV感染下调BST2的表达。我们进一步发现，乙脑病毒包膜蛋白E显著下调BST2，而其他病毒成分不下调，病毒蛋白M在这一过程中起辅助作用。包膜蛋白e介导的BST2下调似乎经历了溶酶体降解途径。进一步的研究表明，BST2的跨膜结构域和螺旋结构域（CC）是病毒蛋白E的靶结构域，而BST2的N端和c端膜锚点和CC结构域是阻断乙脑病毒释放所必需的。我们的研究结果表明，包膜病毒出芽发生在细胞内隔室的释放可以被BST2限制。
It has been well documented that BST2 restricts the release of enveloped viruses by cross-linking newly produced virions to the cell membrane. However, it is less clear whether and how BST2 inhibits the release of enveloped viruses which bud via the secretory pathway. Here, we demonstrated that BST2 restricts the release of Japanese encephalitis virus (JEV) whose budding occurs at the ER-Golgi intermediate compartment, and in turn, JEV infection downregulates BST2 expression. We further found that the JEV envelope protein E, but not other viral components, significantly downregulates BST2 with the viral protein M playing an auxiliary role in the process. Envelope protein E-mediated BST2 downregulation appears to undergo lysosomal degradation pathway. Additional study revealed that the transmembrane domain and the coiled-coil domain (CC) of BST2 are the target domains of viral protein E and that the N- and C-terminal membrane anchors and the CC domain of BST2 are essential for blocking JEV release. Our results together indicate that the release of enveloped viruses whose budding take place in an intracellular compartment can be restricted by BST2.