Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic.
Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic
Proc Natl Acad Sci U S A. 2021 May 11;118(19). doi: 10.1073/pnas.2024251118.
Most rhinoviruses, which are the leading cause of the common cold, utilize intercellular adhesion molecule-1 (ICAM-1) as a receptor to infect cells. To release their genomes, rhinoviruses convert to activated particles that contain pores in the capsid, lack minor capsid protein VP4, and have an altered genome organization. The binding of rhinoviruses to ICAM-1 promotes virus activation; however, the molecular details of the process remain unknown. Here, we present the structures of virion of rhinovirus 14 and its complex with ICAM-1 determined to resolutions of 2.6 and 2.4 Å, respectively. The cryo-electron microscopy reconstruction of rhinovirus 14 virions contains the resolved density of octanucleotide segments from the RNA genome that interact with VP2 subunits. We show that the binding of ICAM-1 to rhinovirus 14 is required to prime the virus for activation and genome release at acidic pH. Formation of the rhinovirus 14-ICAM-1 complex induces conformational changes to the rhinovirus 14 capsid, including translocation of the C termini of VP4 subunits, which become poised for release through pores that open in the capsids of activated particles. VP4 subunits with altered conformation block the RNA-VP2 interactions and expose patches of positively charged residues. The conformational changes to the capsid induce the redistribution of the virus genome by altering the capsid-RNA interactions. The restructuring of the rhinovirus 14 capsid and genome prepares the virions for conversion to activated particles. The high-resolution structure of rhinovirus 14 in complex with ICAM-1 explains how the binding of uncoating receptors enables enterovirus genome release.
大多数引发普通感冒的鼻病毒（rhinovirus）利用细胞间黏附分子-1（ICAM-1）作为受体来感染细胞。为了释放其基因组，鼻病毒转化为激活的颗粒，这些颗粒在衣壳中包含孔，缺乏次要衣壳蛋白 VP4，并且具有改变的基因组组织。鼻病毒与 ICAM-1 的结合促进病毒激活；然而，该过程的分子细节仍不清楚。在这里，我们展示了测定分辨率分别为 2.6 和 2.4 Å的鼻病毒 14 病毒粒子及其与 ICAM-1 的复合物的结构。鼻病毒 14 病毒粒子的冷冻电镜重建包含与 VP2 亚基相互作用的 RNA 基因组的八核苷酸片段的解析密度。我们表明，ICAM-1 与鼻病毒 14 的结合对于在酸性 pH 值下为病毒激活和基因组释放做好准备是必需的。鼻病毒 14-ICAM-1 复合物的形成诱导鼻病毒 14 衣壳的构象变化，包括 VP4 亚基的 C 末端的易位，其通过在激活颗粒的衣壳中打开的孔准备释放。具有改变构象的 VP4 亚基阻止 RNA-VP2 相互作用并暴露带正电荷的残基的斑块。衣壳的构象变化通过改变衣壳-RNA 相互作用来诱导病毒基因组的重新分布。鼻病毒 14 衣壳和基因组的结构重排使病毒粒子准备转化为激活颗粒。与 ICAM-1 复合的鼻病毒 14 的高分辨率结构解释了脱壳受体的结合如何使肠道病毒基因组释放。
