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Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM.
PLOS Biology ( IF 7.8 ) Pub Date : 2020-03-31 , DOI: 10.1371/journal.pbio.3000649
Joseph S Snowden 1 , Daniel L Hurdiss 1 , Oluwapelumi O Adeyemi 1 , Neil A Ranson 1 , Morgan R Herod 1 , Nicola J Stonehouse 1
Affiliation  

Icosahedral viral capsids must undergo conformational rearrangements to coordinate essential processes during the viral life cycle. Capturing such conformational flexibility has been technically challenging yet could be key for developing rational therapeutic agents to combat infections. Noroviruses are nonenveloped, icosahedral viruses of global importance to human health. They are a common cause of acute gastroenteritis, yet no vaccines or specific antiviral agents are available. Here, we use genetics and cryo-electron microscopy (cryo-EM) to study the high-resolution solution structures of murine norovirus as a model for human viruses. By comparing our 3 structures (at 2.9- to 3.1-Å resolution), we show that whilst there is little change to the shell domain of the capsid, the radiating protruding domains are flexible, adopting distinct states both independently and synchronously. In doing so, the capsids sample a range of conformational space, with implications for maintaining virion stability and infectivity.



中文翻译:

高分辨率低温 EM 显示的小鼠诺瓦克病毒衣壳的动力学。

二十面体病毒衣壳必须进行构象重排以协调病毒生命周期中的基本过程。捕捉这种构象的灵活性在技术上具有挑战性,但可能是开发合理的治疗剂来对抗感染的关键。诺如病毒是对人类健康具有全球重要性的无包膜二十面体病毒。它们是急性胃肠炎的常见原因,但尚无可用的疫苗或特定的抗病毒药物。在这里,我们使用遗传学和低温电子显微镜 (cryo-EM) 来研究鼠类诺如病毒的高分辨率溶液结构,以此作为人类病毒的模型。通过比较我们的 3 种结构(在 2.9 到 3.1-Å 分辨率下),我们表明虽然衣壳的壳域几乎没有变化,但辐射突出域是灵活的,独立地和同步地采用不同的状态。在这样做的过程中,衣壳对一系列构象空间进行采样,这对维持病毒粒子的稳定性和传染性具有重要意义。

更新日期:2020-03-31
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