Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury
Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury
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DOI：
10.1038/78654
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发表时间：
2000-08-01
期刊：
影响因子：
82.9
通讯作者：
Nabel, GJ
中科院分区：
文献类型：
--
作者：
Yang, ZY;Duckers, HJ;Nabel, GJ
在这里，我们定义了埃博拉病毒致病性的主要病毒决定因素；埃博拉病毒扎伊尔病毒颗粒糖蛋白（CP）的合成在体外和体内诱导人内皮细胞的细胞毒性作用。这种效应映射到这种 I 型跨膜糖蛋白（该病毒的七个基因产物之一）的富含丝氨酸-苏氨酸的粘蛋白样结构域。将 GP 基因转移到移植的人或猪血管中会在 48 小时内引起大量内皮细胞损失，从而导致血管通透性大幅增加。删除 GP 的粘蛋白样区域可以消除这些效应，而不影响蛋白质的表达或功能。源自雷斯顿病毒株的CP不会破坏人类血管的脉管系统，该病毒会在非人类灵长类动物中引起疾病，但不会在人类中引起疾病。相比之下，扎伊尔 CP 会在非人灵长类动物和人类血管中诱导内皮细胞破坏和细胞毒性，而这种作用需要粘蛋白结构域。这些发现表明，CP 通过其粘蛋白结构域是埃博拉病毒致病性的决定因素，并可能导致感染期间的出血。
Here we defined the main viral determinant of Ebola virus pathogenicity; synthesis of the virion glycoprotein (CP) of Ebola virus Zaire induced cytotoxic effects in human endothelial cells in vitro and in vivo. This effect mapped to a serine-threonine-rich, mucin-like domain of this type I transmembrane glycoprotein, one of seven gene products of the virus. Gene transfer of GP into explanted human or porcine blood vessels caused massive endothelial cell loss within 48 hours that led to a substantial increase in vascular permeability. Deletion of the mucin-like region of GP abolished these effects without affecting protein expression or function. CP derived from the Reston strain of virus, which causes disease in nonhuman primates but not in man, did not disrupt the vasculature of human blood vessels. In contrast, the Zaire CP induced endothelial cell disruption and cytotoxicity in both nonhuman primate and human blood vessels, and the mucin domain was required for this effect. These findings indicate that CP, through its mucin domain, is the viral determinant of Ebola pathogenicity and likely contributes to hemorrhage during infection.