National Institute for Physiological Sciences, Okazaki, Japan.
Laboratory of Viral Infection I, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
PLoS Pathog. 2020 Jul 2;16(7):e1008619. doi: 10.1371/journal.ppat.1008619. eCollection 2020 Jul.
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.
诺如病毒是全球范围内引起流行性非细菌性肠胃炎的主要原因。由于缺乏有关感染和复制机制的结构信息，因此难以开发有效的疫苗和治疗方法。在这里，我们使用冷冻电子显微镜显示，鼠诺如病毒的衣壳结构会响应水相条件而发生变化。通过扭转连接两个结构域的柔性铰链，在 pH 值较高的溶液中，突起（P）结构域可可逆地从壳（S）结构域上抬起，但在 pH 值较低的溶液中则位于 S 结构域上。金属离子在此过程中有助于稳定静止构象。此外，在静止构象中，细胞受体 CD300lf 易于接近，因此感染效率大大提高。在人类诺如病毒 GII.3 衣壳中也同时发现了两种类似的 P 结构域构象，尽管构象变化的机制尚不清楚。这些结果为非包膜诺如病毒通过胃肠道中的剧烈环境变化入侵宿主细胞、复制以及有时逃避宿主免疫系统的传播机制提供了新的见解。
