Less Is More: Ebola Virus Surface Glycoprotein Expression Levels Regulate Virus Production and Infectivity
Less Is More: Ebola Virus Surface Glycoprotein Expression Levels Regulate Virus Production and Infectivity
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DOI：
10.1128/jvi.01810-14
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发表时间：
2015-01-01
影响因子：
5.4
通讯作者：
Yang, Chinglai
中科院分区：
文献类型：
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作者：
Mohan, Gopi S.;Ye, Ling;Yang, Chinglai
埃博拉病毒表面糖蛋白(GP(1，2))介导宿主细胞的附着和融合，是宿主中和抗体的主要靶点。Gp(1，2)的高水平表达破坏了正常的细胞生理，而EBOV使用RNA编辑机制来调节gp基因的表达。在这项研究中，我们证明了高水平的GP(1，2)表达会损害EBOV病毒样颗粒(VLP)的产生和释放，以及GP(1，2)假型病毒的感染性。我们进一步证明了这一效应是通过两种机制来实现的。首先，高水平的GP(1，2)表达减少了病毒组装所需的其他蛋白质的合成。其次，含有高水平GP(1，2)的病毒本质上传染性较低，可能是由于受体结合或内体加工受损所致。重要的是，蛋白降解可以挽救高GP(1，2)病毒的传染性。综上所述，我们的研究结果表明，GP(1，2)的表达水平对影响病毒适合性的因素具有深远的影响，RNA编辑可能是EBOV调节GP(1，2)表达以优化病毒产量和感染性的重要机制。EBOV表面糖蛋白(GP(1，2))在病毒感染和致病过程中起重要作用，在病毒复制过程中其表达受RNA编辑机制的严格调控。我们的研究表明，GP(1，2)的表达水平深刻地影响病毒颗粒的产生和释放，并揭示了一种新的机制，即通过GP(1，2)的表达水平来调节埃博拉病毒的传染性。这些发现扩大了我们对EBOV感染和复制在宿主环境适应中的理解，这将有助于制定预防EBOV感染的对策。
The Ebola virus (EBOV) surface glycoprotein (GP(1,2)) mediates host cell attachment and fusion and is the primary target for host neutralizing antibodies. Expression of GP(1,2) at high levels disrupts normal cell physiology, and EBOV uses an RNA-editing mechanism to regulate expression of the GP gene. In this study, we demonstrate that high levels of GP(1,2) expression impair production and release of EBOV virus-like particles (VLPs) as well as infectivity of GP(1,2)-pseudotyped viruses. We further show that this effect is mediated through two mechanisms. First, high levels of GP(1,2) expression reduce synthesis of other proteins needed for virus assembly. Second, viruses containing high levels of GP(1,2) are intrinsically less infectious, possibly due to impaired receptor binding or endosomal processing. Importantly, proteolysis can rescue the infectivity of high-GP(1,2)-containing viruses. Taken together, our findings indicate that GP(1,2) expression levels have a profound effect on factors that contribute to virus fitness and that RNA editing may be an important mechanism employed by EBOV to regulate GP(1,2) expression in order to optimize virus production and infectivity.IMPORTANCE The Ebola virus (EBOV), as well as other members of the Filoviridae family, causes severe hemorrhagic fever that is highly lethal, with up to 90% mortality. The EBOV surface glycoprotein (GP(1,2)) plays important roles in virus infection and pathogenesis, and its expression is tightly regulated by an RNA-editing mechanism during virus replication. Our study demonstrates that the level of GP(1,2) expression profoundly affects virus particle production and release and uncovers a new mechanism by which Ebola virus infectivity is regulated by the level of GP(1,2) expression. These findings extend our understanding of EBOV infection and replication in adaptation of host environments, which will aid the development of countermeasures against EBOV infection.