Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington, United States of America.
PLoS Pathog. 2024 Sep 19;20(9):e1012511. doi: 10.1371/journal.ppat.1012511. eCollection 2024 Sep.
Molecular details of genome packaging are little understood for the majority of viruses. In enteroviruses (EVs), cleavage of the structural protein VP0 into VP4 and VP2 is initiated by the incorporation of RNA into the assembling virion and is essential for infectivity. We have applied a combination of bioinformatic, molecular and structural approaches to generate the first high-resolution structure of an intermediate in the assembly pathway, termed a provirion, which contains RNA and intact VP0. We have demonstrated an essential role of VP0 E096 in VP0 cleavage independent of RNA encapsidation and generated a new model of capsid maturation, supported by bioinformatic analysis. This provides a molecular basis for RNA-dependence, where RNA induces conformational changes required for VP0 maturation, but that RNA packaging itself is not sufficient to induce maturation. These data have implications for understanding production of infectious virions and potential relevance for future vaccine and antiviral drug design.
大多数病毒的基因组包装分子细节还不太清楚。在肠道病毒（EVs）中，结构蛋白 VP0 被切割成 VP4 和 VP2，这一过程是由 RNA 进入正在组装的病毒粒子引发的，对于感染性是必不可少的。我们应用了生物信息学、分子和结构方法的组合，生成了第一个组装途径中间产物的高分辨率结构，称为前病毒，它包含 RNA 和完整的 VP0。我们已经证明了 VP0 E096 在 RNA 包封之外对 VP0 切割的重要作用，并通过生物信息学分析生成了一个新的衣壳成熟模型。这为 RNA 依赖性提供了分子基础，其中 RNA 诱导 VP0 成熟所需的构象变化，但 RNA 包装本身不足以诱导成熟。这些数据对于理解传染性病毒粒子的产生具有重要意义，并且可能对未来的疫苗和抗病毒药物设计具有潜在的相关性。
