Nature 中文 · 2010/12/02
阿尔法病毒是重要动物和人类病原体,而且是可以致命的,如由蚊子传播的Chikungunya病毒所造成的感染最近在印度和东南亚的爆发所表明的那样。阿尔法病毒的E1 和 E2糖蛋白在这种病毒感染宿主细胞的方式中居中心地位。形成病毒表面上尖状物的E1/E2异二聚体在宿主细胞内部囊泡中的微

阿尔法病毒是重要动物和人类病原体,而且是可以致命的,如由蚊子传播的Chikungunya病毒所造成的感染最近在印度和东南亚的爆发所表明的那样。阿尔法病毒的E1 和 E2糖蛋白在这种病毒感染宿主细胞的方式中居中心地位。形成病毒表面上尖状物的E1/E2异二聚体在宿主细胞内部囊泡中的微酸性条件下会分解,E1通过与核内体膜融合来触发感染。Félix Rey及其同事介绍了在中性pH值下Chikungunya病毒包膜糖蛋白的结构;Michael Rossmann及其同事介绍了另一种阿尔法病毒、即人类“辛德毕斯热”致病病毒的包膜糖蛋白在低pH值下的结构。对两种结构所做的对比为这种融合激发是怎样被控制的提供了线索,也指出了可能的疫苗作用目标。



Nature doi:10.1038/nature09546

Structural changes of envelope proteins during alphavirus fusion

Long Li,Joyce Jose,Ye Xiang,Richard J. Kuhn" Michael G. Rossmann

Alphaviruses are enveloped RNA viruses that have a diameter of about 700?? and can be lethal human pathogens1. Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2–E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface1, 2, 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with T = 4 quasi-symmetry. The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion3, 4. The E2 protein is responsible for receptor binding5, 6 and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm3, 4. Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2–E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino- and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2.

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