美国加州大学Z. Hong Zhou团队近期取得重要工作进展，他们研究提出在宿主细胞中可视化蓝舌病毒的RNA基因组包装和囊膜组装。相关研究成果2024年4月12日在线发表于《细胞》杂志上。

与双链DNA（dsDNA）、单链DNA（ssDNA）和ssRNA病毒不同，人们对dsRNA病毒的基因组包装机制知之甚少。

研究人员结合了高分辨率冷冻电镜（cryo-EM）、细胞冷冻电子断层扫描（cryoET）和结构导向诱变技术，研究了蓝舌病毒（BTV）的基因组包装和衣壳组装，蓝舌病毒是双链核糖核酸病毒Reoviride家族的一员。共捕获了11种BTV衣壳的组装状态，分辨率高达2.8Å，其中大多数在宿主细胞质中可见。在衣壳蛋白VP3的顶点下方发现了ATPase VP6，它是一种携带RNA的五聚体，有助于RNA的包装。RNA包装使VP3外壳扩展，然后与中间层和外层蛋白质结合，产生感染性病毒粒子。

总之，这一研究揭示的BTV组装机制的“双重性”特征调和了以前相互矛盾的共组装和核心填充模型，并为Reoviridae（呼肠病毒）成员及其他成员的神秘RNA包装和衣壳组装提供了见解。

附：英文原文

Title: RNA genome packaging and capsid assembly of bluetongue virus visualized in host cells

Author: Xian Xia, Po-Yu Sung, Michael W. Martynowycz, Tamir Gonen, Polly Roy, Z. Hong Zhou

Issue&Volume: 2024-04-12

Abstract: Unlike those of double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and ssRNAviruses, the mechanism of genome packaging of dsRNA viruses is poorly understood.Here, we combined the techniques of high-resolution cryoelectron microscopy (cryo-EM),cellular cryoelectron tomography (cryo-ET), and structure-guided mutagenesis to investigategenome packaging and capsid assembly of bluetongue virus (BTV), a member of the Reoviridae family of dsRNA viruses. A total of eleven assembly states of BTV capsid were captured,with resolutions up to 2.8 , with most visualized in the host cytoplasm. ATPase VP6was found underneath the vertices of capsid shell protein VP3 as an RNA-harboringpentamer, facilitating RNA packaging. RNA packaging expands the VP3 shell, which thenengages middle- and outer-layer proteins to generate infectious virions. These revealed“duality” characteristics of the BTV assembly mechanism reconcile previous contradictoryco-assembly and core-filling models and provide insights into the mysterious RNA packagingand capsid assembly of Reoviridae members and beyond.

DOI: 10.1016/j.cell.2024.03.007

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00299-X