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ICAM-1 induced rearrangements of capsid and genome prime rhinovirus 14 for activation and uncoating [Microbiology]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-05-11 , DOI: 10.1073/pnas.2024251118
Dominik Hrebík 1 , Tibor Füzik 1 , Mária Gondová 1 , Lenka Šmerdová 1 , Athanassios Adamopoulos 1 , Ondrej Šedo 1 , Zbyněk Zdráhal 1 , Pavel Plevka 2
Affiliation  

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.



中文翻译:

ICAM-1 诱导衣壳和基因组初始鼻病毒 14 的重排以激活和脱壳 [微生物学]

大多数鼻病毒是普通感冒的主要原因,它们利用细胞间粘附分子 1 (ICAM-1) 作为受体来感染细胞。为了释放它们的基因组,鼻病毒转化为活性颗粒,这些颗粒在衣壳中含有孔,缺乏次要衣壳蛋白 VP4,并具有改变的基因组结构。鼻病毒与 ICAM-1 的结合促进了病毒的激活;然而,该过程的分子细节仍然未知。在这里,我们展示了鼻病毒 14 的病毒粒子结构及其与 ICAM-1 的复合物,分辨率分别为 2.6 和 2.4 Å。鼻病毒 14 病毒体的冷冻电子显微镜重建包含与 VP2 亚基相互作用的 RNA 基因组中八核苷酸片段的解析密度。我们表明 ICAM-1 与鼻病毒 14 的结合是在酸性 pH 下激活病毒和释放基因组所必需的。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,其准备通过在活化颗粒衣壳中打开的孔释放。具有改变构象的 VP4 亚基会阻断 RNA-VP2 相互作用并暴露带正电荷残基的斑块。衣壳的构象变化通过改变衣壳-RNA 相互作用诱导病毒基因组的重新分布。鼻病毒 14 衣壳和基因组的重组为病毒粒子转化为活化颗粒做好了准备。

更新日期:2021-05-05
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