Vaccinia virus egress mediated by virus protein A36 is reliant on the F12 protein
Vaccinia virus egress mediated by virus protein A36 is reliant on the F12 protein
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DOI：
10.1099/jgv.0.000816
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发表时间：
2017-06-01
影响因子：
3.8
通讯作者：
Smith, Geoffrey L.
中科院分区：
文献类型：
--
作者：
Carpentier, David C. J.;Van Loggerenberg, Alexander;Smith, Geoffrey L.
牛痘病毒从其宿主细胞中的逃逸是由微管相关的运动驱动蛋白1介导的，并且三种病毒蛋白A36和F12/E2复合物涉及该过程。F12表达的缺失导致比A36缺失更严重的出口减少，但这些蛋白质是否参与驱动蛋白-1募集的相同或不同机制尚不清楚。在这里，它表明，一个病毒缺乏这两种蛋白质形成一个较小的空斑比突变体缺乏任何一个基因单独，表明非冗余功能。A36不仅将病毒体直接连接到驱动蛋白-1，而且使肌动蛋白聚合成核以推动表面病毒体远离宿主细胞。为了解决这些功能对病毒传播的相对重要性，构建了一组重组病毒，其中A36结合驱动蛋白-1或使肌动蛋白聚合成核的能力在存在或不存在F12表达的情况下单独或一起被废除。这些病毒的分析表明，在F12蛋白的存在下，驱动蛋白-1相互作用的损失作出了更大的贡献比形成肌动蛋白尾巴的空斑大小。然而，在不存在F12的情况下，A36促进排出的能力被废除。因此，A36促进驱动蛋白-1排出的能力依赖于F12蛋白。
Egress of vaccinia virus from its host cell is mediated by the microtubule-associated motor kinesin-1, and three viral proteins, A36 and the F12/E2 complex, have been implicated in this process. Deletion of F12 expression causes a more severe reduction in egress than deletion of A36 but whether these proteins are involved in the same or different mechanisms of kinesin-1 recruitment is unknown. Here it is shown that a virus lacking both proteins forms a smaller plaque than mutants lacking either gene alone, indicating non-redundant functions. A36 not only links virions directly to kinesin-1 but also nucleates actin polymerization to propel surface virions away from the host cell. To address the relative importance of these functions for virus spread, a panel of recombinant viruses was constructed in which the ability of A36 to bind kinesin-1 or to nucleate actin polymerization was abrogated individually or together, in the presence or absence of F12 expression. Analysis of these viruses revealed that in the presence of the F12 protein, loss of kinesin-1 interaction made a greater contribution to plaque size than did the formation of actin tails. However in the absence of F12, the ability of A36 to promote egress was abrogated. Therefore, the ability of A36 to promote egress by kinesin-1 is reliant on the F12 protein.