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.
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8017-8022. doi: 10.1073/pnas.1707369114. Epub 2017 Jul 10.
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.
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。
