由蚊子传播的裂谷热病毒（Rift Valley fever virus, RVFV）在非洲的牲畜中导致流行病，并且对人类也是致命性的。如今，在一项新的研究中，来自法国国家科研中心（CNRS）、巴斯德研究所、德国哥廷根大学和荷兰乌特勒支大学的研究人员描述了这种病毒将它的一种包膜蛋白插入到宿主细胞膜中从而使得它能够感染宿主细胞的机制。他们证实这种病毒包膜蛋白具有一种特异性地识别细胞膜中的一类脂质的“口袋”。这种口袋也在由不同蚊子传播的其他的人致病性病毒（如寨卡病毒和基孔肯雅病毒）中发现到。理解这些相互作用应当为鉴定出靶向这些蚊媒传播病毒的新治疗策略铺平道路。相关研究结果发表在2017年11月3日的Science期刊上，论文标题为“A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion”。论文通信作者为巴斯德研究所结构病毒学部门的Félix Rey、P. Guardado-Calvo和哥廷根大学的J. S. Hub。
作者: ipsvirus 时间: 2017-11-19 11:30 A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion
P. Guardado-Calvo1,2,*, K. Atkovska3, S. A. Jeffers1,2,†, N. Grau1,2,‡, M. Backovic1,2, J. Pérez-Vargas1,2,‡, S. M. de Boer4,§, M. A. Tortorici1,2, G. Pehau-Arnaudet5, J. Lepault6, P. England5,7, P. J. Rottier4, B. J. Bosch4, J. S. Hub3,*, F. A. Rey1,2,*
The Rift Valley fever virus (RVFV) is transmitted by infected mosquitoes, causing severe disease in humans and livestock across Africa. We determined the x-ray structure of the RVFV class II fusion protein Gc in its postfusion form and in complex with a glycerophospholipid (GPL) bound in a conserved cavity next to the fusion loop. Site-directed mutagenesis and molecular dynamics simulations further revealed a built-in motif allowing en bloc insertion of the fusion loop into membranes, making few nonpolar side-chain interactions with the aliphatic moiety and multiple polar interactions with lipid head groups upon membrane restructuring. The GPL head-group recognition pocket is conserved in the fusion proteins of other arthropod-borne viruses, such as Zika and chikungunya viruses, which have recently caused major epidemics worldwide.
