Recovery of infectious Ebola virus from complementary DNA:: RNA editing of the GP gene and viral cytotoxicity

Recovery of infectious Ebola virus from complementary DNA:: RNA editing of the GP gene and viral cytotoxicity
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DOI:
10.1126/science.1057269
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发表时间:
2001-03-09
期刊:
影响因子:
56.9
通讯作者:
Klenk, HD
Klenk, HD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Volchkov, VE;Volchkova, VA;Klenk, HD

文献摘要

被引文献

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为了研究埃博拉病毒高致病性的机制,我们建立了一个系统,允许从克隆的cDNA中回收感染性病毒,从而允许遗传操作。我们创建了一个突变体,其中编码包膜糖蛋白(CP)的基因的编辑位点被消除。该突变体不再表达非结构糖蛋白sGP,CP合成增加,但大部分以未成熟前体形式积累在内质网中。突变体的细胞毒性显著高于野生型病毒,表明CP引起的细胞毒性通过转录RNA编辑和sGP表达被病毒下调。
To study the mechanisms underlying the high pathogenicity of Ebola virus, we have established a system that allows the recovery of infectious virus from cloned cDNA and thus permits genetic manipulation. We created a mutant in which the editing site of the gene encoding envelope glycoprotein (CP) was eliminated. This mutant no longer expressed the nonstructural glycoprotein sGP, Synthesis of CP increased, but most of it accumulated in the endoplasmic reticulum as immature precursor. The mutant was significantly more cytotoxic than wild-type virus, indicating that cytotoxicity caused by CP is down-regulated by the virus through transcriptional RNA editing and expression of sGP.