Program in Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Program in Molecular Biophysics, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Structure. 2020 Aug 4;28(8):888-896.e3. doi: 10.1016/j.str.2020.04.016. Epub 2020 May 14.
Non-enveloped icosahedral double-stranded RNA (dsRNA) viruses possess multifunctional capsids required for their proliferation. Whereas protozoan/fungal dsRNA viruses have a relatively simple capsid structure, which suffices for the intracellular phase in their life cycle, metazoan dsRNA viruses have acquired additional structural features as an adaptation for extracellular cell-to-cell transmission in multicellular hosts. Here, we present the first atomic model of a metazoan dsRNA totivirus-like virus and the structure reveals three unique structural traits: a C-terminal interlocking arm, surface projecting loops, and an obstruction at the pore on the 5-fold symmetry axis. These traits are keys to understanding the capsid functions of metazoan dsRNA viruses, such as particle stability and formation, cell entry, and endogenous intraparticle transcription of mRNA. On the basis of molecular dynamics simulations of the obstructed pore, we propose a possible mechanism of intraparticle transcription in totivirus-like viruses, which dynamically switches between open and closed states of the pore(s).
无包膜二十面体双链 RNA (dsRNA) 病毒具有多功能衣壳，这些衣壳对于其增殖是必需的。虽然原生动物/真菌 dsRNA 病毒具有相对简单的衣壳结构，足以满足其生命周期中的细胞内阶段，但后生动物 dsRNA 病毒已经获得了额外的结构特征，以适应在多细胞宿主中的细胞间的细胞外传播。在这里，我们呈现了第一个后生动物 dsRNA 呼肠孤病毒样病毒的原子模型，该结构揭示了三个独特的结构特征：C 末端互锁臂、表面突出环和 5 重对称轴上孔的障碍物。这些特征是理解后生动物 dsRNA 病毒的衣壳功能的关键，例如颗粒稳定性和形成、细胞进入以及内源性颗粒内 mRNA 的转录。基于受阻孔的分子动力学模拟，我们提出了呼肠孤病毒样病毒中颗粒内转录的可能机制，其中孔（s）的开放和关闭状态之间动态切换。
