Expression of Ebolavirus glycoprotein on the target cells enhances viral entry.
Expression of Ebolavirus glycoprotein on the target cells enhances viral entry.
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DOI：
10.1186/1743-422x-6-75
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发表时间：
2009-06-08
期刊：
影响因子：
4.8
通讯作者：
Rong L
中科院分区：
文献类型：
--
作者：
Manicassamy B;Rong L
埃博拉病毒进入靶细胞由病毒糖蛋白GP介导。天然GP作为病毒体上的同源三聚体存在，并且含有两个亚基，参与受体结合的表面亚基（GP 1）和介导病毒-宿主膜融合的跨膜亚基（GP 2）。以前，我们发现GP在靶细胞上的过表达阻断了GP介导的病毒进入，这很可能是由于GP 1的受体干扰。在这项研究中，使用四环素诱导系统，我们报告说，低水平的GP表达的靶细胞，而不是干扰，特别是增强GP介导的病毒进入。详细的映射分析强烈表明，融合亚基GP 2是主要负责这种新的现象，在这里被称为反式增强。我们的数据表明，GP 2介导的反式增强病毒融合发生的机制类似于真核细胞膜融合过程，涉及特定的反式寡聚化和融合介质的合作相互作用。这些发现对我们目前对病毒进入和重复感染干扰的理解具有重要意义。
Entry of Ebolavirus to the target cells is mediated by the viral glycoprotein GP. The native GP exists as a homotrimer on the virions and contains two subunits, a surface subunit (GP1) that is involved in receptor binding and a transmembrane subunit (GP2) that mediates the virus-host membrane fusion. Previously we showed that over-expression of GP on the target cells blocks GP-mediated viral entry, which is mostly likely due to receptor interference by GP1. In this study, using a tetracycline inducible system, we report that low levels of GP expression on the target cells, instead of interfering, specifically enhance GP mediated viral entry. Detailed mapping analysis strongly suggests that the fusion subunit GP2 is primarily responsible for this novel phenomenon, here referred to as trans enhancement. Our data suggests that GP2 mediated trans enhancement of virus fusion occurs via a mechanism analogous to eukaryotic membrane fusion processes involving specific trans oligomerization and cooperative interaction of fusion mediators. These findings have important implications in our current understanding of virus entry and superinfection interference.