Dynamic rotation of the protruding domain enhances the infectivity of norovirus
Dynamic rotation of the protruding domain enhances the infectivity of norovirus
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DOI：
10.1371/journal.ppat.1008619
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发表时间：
2020-07-01
期刊：
影响因子：
6.7
通讯作者：
Murata, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Song, Chihong;Takai-Todaka, Reiko;Murata, Kazuyoshi
据报道，杯状病毒的衣壳结构根据种类和基因型分为两种不同类型。一种是P结构域的上升型构象，如人诺如病毒G2 10和兔出血症病毒所示，P结构域从S结构域表面上升。另一种是如人诺如病毒GI.1、SAP病毒和生米格尔海狮病毒所示的P结构域的休止型构象，P结构域位于S结构域上。在这里，我们证明了小鼠诺如病毒的P结构域在上升和静止的P结构域构象类型之间可逆地改变，以响应水的条件。我们还同时在人诺如病毒GII-3VLP中发现了相似的两个P结构域构象。我们的发现为杯状病毒的病毒感染机制提供了新的见解。诺如病毒是全球流行性非细菌性胃肠炎的主要原因。缺乏关于感染和复制机制的结构性信息阻碍了有效疫苗和补救措施的开发。在这里，使用冷冻电子显微镜，我们显示了小鼠诺如病毒的衣壳结构随着水条件的变化而变化。通过扭转连接两个结构域的柔性铰链，在较高pH的溶液中，突出的(P)结构域可逆地从壳(S)结构域上升，但在较低pH的溶液中，突出的(P)结构域停留在S结构域上。在这一过程中，金属离子有助于稳定静止构象。此外，在静止构象中，细胞受体CD300lf很容易获得，从而显著提高了感染效率。在人诺如病毒GII-3衣壳中也同时发现了两个类似的P结构域构象，尽管构象变化的机制尚不清楚。这些结果为诺沃克病毒的无包膜传播机制提供了新的见解。诺沃克病毒通过胃肠道环境的戏剧性变化入侵宿主细胞、复制，有时还逃避宿主免疫系统。
Author summary The capsid structure of caliciviruses has been reported to be classified into two different types, according to the species and genotype. One is the rising type of P domain conformation as shown in human norovirus GII.10 and rabbit hemorrhagic disease virus (RHDV), where the P domain rises from the S domain surface. The other is the resting type of P domain conformation as shown in human norovirus GI.1, sapovirus and San Miguel sea lion virus (SMSV), where the P domain rests upon the S domain. Here, we demonstrate that the P domain of the murine noroviruses changes reversibly between the rising and resting P domain conformation types in response to aqueous conditions. We also found the similar two P domain conformations in human norovirus GII.3 VLPs at the same time. Our findings provide new insights into the mechanisms of viral infection of caliciviruses.Norovirus is the major cause of epidemic nonbacterial gastroenteritis worldwide. Lack of structural information on infection and replication mechanisms hampers the development of effective vaccines and remedies. Here, using cryo-electron microscopy, we show that the capsid structure of murine noroviruses changes in response to aqueous conditions. By twisting the flexible hinge connecting two domains, the protruding (P) domain reversibly rises off the shell (S) domain in solutions of higher pH, but rests on the S domain in solutions of lower pH. Metal ions help to stabilize the resting conformation in this process. Furthermore, in the resting conformation, the cellular receptor CD300lf is readily accessible, and thus infection efficiency is significantly enhanced. Two similar P domain conformations were also found simultaneously in the human norovirus GII.3 capsid, although the mechanism of the conformational change is not yet clear. These results provide new insights into the mechanisms of non-enveloped norovirus transmission that invades host cells, replicates, and sometimes escapes the hosts immune system, through dramatic environmental changes in the gastrointestinal tract.