抗体诱导的人鼻病毒 B14 脱壳。
Antibody-induced uncoating of human rhinovirus B14.
机构信息
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
Department of Microbiology, Faculty of Preclinical Medicine, Fourth Military Medical University, Xi'an 710032, China.
出版信息
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8017-8022. doi: 10.1073/pnas.1707369114. Epub 2017 Jul 10.
Abstract
Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody-virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.
摘要
鼻病毒（RV）是人类普通感冒的主要原因。它们具有无包膜的二十面体衣壳，周围环绕着正链 RNA 基因组。在这里，我们报告说，中和抗体（C5）的抗原结合（Fab）片段可以触发 RV-B14 基因组的释放，形成空衣壳颗粒并中和病毒感染。使用冷冻电子显微镜，已经分别以 2.3Å 和 3.0Å 的分辨率确定了 C5 Fab 与完整和空衣壳颗粒复合物的结构。每个 60 个 Fab 分子主要结合在病毒蛋白 3（VP3）上的一个区域。C5 Fab 与 RV-B14 的结合导致衣壳上孔周围的构象发生显著变化，病毒 RNA 可能通过这些孔离开。到目前为止，这些结果是抗体-病毒复合物的最高分辨率视图，并阐明了抗体通过诱导病毒脱壳来中和 RV 和相关病毒的机制。
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