Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol
Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol
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DOI：
10.1038/ncomms8688
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发表时间：
2015-07-01
影响因子：
16.6
通讯作者：
Ernst, Andreas M.
中科院分区：
文献类型：
--
作者：
Hacke, Moritz;Bjorkholm, Patrik;Ernst, Andreas M.
埃博拉病毒的高致病性反映了多个同时发生的感染过程。除其他重要决定因素外，埃博拉融合原糖蛋白（GP）与感染细胞脱离有关，并最终导致血管渗漏和出血热。在这里，我们报告了膜锚定的GP足以诱导贴壁细胞脱离。结果表明，通过全长GP（1,2）或亚基GP(2)诱导的脱离取决于胆固醇和跨膜结构域的结构。这些数据揭示了GP调节埃博拉病毒组装的一种新的分子机制，并提示降胆固醇药物可作为对抗GP介导的细胞脱离的治疗药物。
The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP(1,2) or the subunit GP(2) depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment.