Volchkov V E, Volchkova V A, Muhlberger E, Kolesnikova L V, Weik M, Dolnik O, Klenk H D
Institut für Virologie, Philipps-Universität, Robert-Koch-Strasse 17, 35037 Marburg, Germany.
Science. 2001 Mar 9;291(5510):1965-9. doi: 10.1126/science.1057269. Epub 2001 Feb 1.
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 (GP) was eliminated. This mutant no longer expressed the nonstructural glycoprotein sGP. Synthesis of GP 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 GP is down-regulated by the virus through transcriptional RNA editing and expression of sGP.
为了研究埃博拉病毒高致病性的潜在机制，我们建立了一个系统，该系统能够从克隆的cDNA中拯救出感染性病毒，从而实现基因操作。我们构建了一个突变体，其中编码包膜糖蛋白（GP）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。GP的合成增加，但大部分以未成熟前体的形式在内质网中积累。该突变体的细胞毒性明显高于野生型病毒，这表明病毒通过转录RNA编辑和sGP的表达下调了由GP引起的细胞毒性。
