Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus.
Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus.
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DOI：
10.1371/journal.ppat.1006377
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发表时间：
2017-06
期刊：
影响因子：
6.7
通讯作者：
Rossmann MG
中科院分区：
文献类型：
--
作者：
Mangala Prasad V;Klose T;Rossmann MG
怀孕期间的病毒感染是婴儿发病率和死亡率的一个重要原因。其中，风疹病毒感染是一个得到充分证实的导致流产或严重胎儿缺陷的例子。然而，由于病毒粒子的多形性，关于风疹病毒的结构信息一直缺乏。在这里，我们报告了一个螺旋结构的风疹病毒粒子使用冷冻电子断层扫描。表面尖峰的亚断层图像平均确定了病毒糖蛋白的相对位置，这与早期的病毒二十面体模型不同。体外组装的核衣壳和病毒粒子的断层分析为病毒组装提供了模板。对未成熟和成熟病毒粒子的比较表明，糖蛋白中的大量重排可能是形成感染性病毒粒子所必需的。这些结果提供了已知的第一个螺旋膜包裹病毒的例子，同时也为其组装和成熟途径提供了结构基础。风疹病毒(RV)在怀孕期间感染时会导致严重的胎儿缺陷。尽管RV具有重要的医学价值，但由于病毒粒子的不规则形状和大小不一，RV的结构仍然未知。利用冷冻电子断层扫描，我们已经确定了RV的结构，它显示了一个独特的螺旋外表面。随后RV表面尖峰的局部平均建立了其免疫原糖蛋白的构象。对病毒衣壳蛋白的体外组装研究为病毒组装所必需的相互作用提供了洞察力。成熟和未成熟轮状病毒之间的比较显示，病毒粒子结构发生了巨大的构象变化，这是病毒成熟所必需的。这些结果有助于从结构上了解轮状病毒的致病性，这可能也与其他致畸病毒有关。
Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway. Rubella virus (RV) causes serious fetal defects when contracted during pregnancy. Despite its medical importance, due to the irregular shapes and different sizes of the virions, the RV structure has remained unknown. Using cryo-electron tomography, we have determined the RV structure, which shows a unique, helical outer surface. Subsequent local averaging of the RV surface spikes has established the conformations of its immunogenic glycoproteins. In vitro assembly studies on the virus capsid protein have provided insights into the interactions necessary for virus assembly. Comparisons between mature and immature RV show large conformational changes in the virion structure that are essential for virus maturation. These results help to gain a structural understanding of RV pathogenicity, which may also be relevant to other teratogenic viruses.