Antibody-induced uncoating of human rhinovirus B14
Antibody-induced uncoating of human rhinovirus B14
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DOI：
10.1073/pnas.1707369114
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发表时间：
2017-07-25
影响因子：
11.1
通讯作者：
Rossmann, Michael G.
中科院分区：
文献类型：
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作者：
Dong, Yangchao;Liu, Yue;Rossmann, Michael G.
鼻病毒（RV）是人类常见感冒的主要原因。它们有一个无包膜的二十面体衣壳围绕着一个正链RNA基因组。在这里，我们报告了中和抗体（C5）的抗原结合（Fab）片段可以触发RV-B14的基因组释放，形成空颗粒并中和病毒感染。使用冷冻电子显微镜，分别在2.3埃和3.0埃分辨率下确定了与完整和空颗粒复合的C5 Fab的结构。60个Fab分子中的每一个主要结合病毒蛋白3（VP 3）上的区域。C5 Fab与RV-B14的结合导致病毒RNA可能通过其离开的衣壳中的孔周围的显著构象变化。这些结果是迄今为止抗体-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。
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-electronmicroscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 angstrom and 3.0 angstrom 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.