Structural Studies on the Shapeshifting Murine Norovirus.
Structural Studies on the Shapeshifting Murine Norovirus.
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DOI：
10.3390/v13112162
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发表时间：
2021-10-26
期刊：
影响因子：
--
通讯作者：
Smith TJ
中科院分区：
文献类型：
--
作者：
Sherman MB;Williams AN;Smith HQ;Pettitt BM;Wobus CE;Smith TJ
诺如病毒是造成全球近五分之一胃肠炎病例的原因。杯状病毒衣壳由180个拷贝的分子量约为58 kDa的VP 1组成。该外壳蛋白分为N-末端（N）、壳（S）和C-末端突出（P）结构域。S结构域在病毒RNA基因组周围形成壳，而P结构域二聚化以在衣壳表面上形成突起。P结构域被细分为P1和P2亚结构域，后者含有细胞受体和中和抗体的结合位点。本文综述了对鼠诺如病毒（MNV）的研究，表明衣壳响应于几个生理相关的线索;胆汁，pH值，Mg 2+，和Ca 2+。在感染的初始部位，即肠道，高胆汁和金属浓度以及低pH导致两种显著的构象变化：（1）P结构域收缩到壳结构域上，以及（2）P结构域内的几种构象变化导致增强的受体结合，同时阻断抗体中和。相反，pH值为中性，血清中胆汁和金属的浓度较低。在这些条件下，P结构域尖端的环处于开放构象，其中P结构域漂浮在壳上方的接头或系链上。这种构象状态有利于抗体结合，但减少与受体的相互作用。通过这种方式，MNV利用肠道中的代谢物和环境线索来优化细胞附着并逃避抗体结合，但在血清中呈现出与免疫系统完全不同的结构。据我们所知，这是病毒以这种方式变形以逃避免疫反应的第一个例子。
Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. The calicivirus capsid is composed of 180 copies of VP1 with a molecular weight of ~58 kDa. This coat protein is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. The P domain is subdivided into P1 and P2 subdomains, with the latter containing the binding sites for cellular receptors and neutralizing antibodies. Reviewed here are studies on murine norovirus (MNV) showing that the capsid responds to several physiologically relevant cues; bile, pH, Mg2+, and Ca2+. In the initial site of infection, the intestinal tract, high bile and metal concentrations and low pH cause two significant conformational changes: (1) the P domain contracts onto the shell domain and (2) several conformational changes within the P domain lead to enhanced receptor binding while blocking antibody neutralization. In contrast, the pH is neutral, and the concentrations of bile and metals are low in the serum. Under these conditions, the loops at the tip of the P domain are in the open conformation with the P domain floating on a linker or tether above the shell. This conformational state favors antibody binding but reduces interactions with the receptor. In this way, MNV uses metabolites and environmental cues in the intestine to optimize cellular attachment and escape antibody binding but presents a wholly different structure to the immune system in the serum. To our knowledge, this is the first example of a virus shapeshifting in this manner to escape the immune response.
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影响因子：
11.8
作者：
Hall AJ;Lopman BA;Payne DC;Patel MM;Gastañaduy PA;Vinjé J;Parashar UD
通讯作者：
Parashar UD
DOI：
10.1126/science.aaf1220
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Orchard RC;Wilen CB;Doench JG;Baldridge MT;McCune BT;Lee YC;Lee S;Pruett-Miller SM;Nelson CA;Fremont DH;Virgin HW
通讯作者：
Virgin HW
影响因子：
11.8
作者：
Costantini V;Morantz EK;Browne H;Ettayebi K;Zeng XL;Atmar RL;Estes MK;Vinjé J
通讯作者：
Vinjé J
影响因子：
6.4
作者：
Blanton, LH;Adams, SM;Monroe, SS
通讯作者：
Monroe, SS
影响因子：
3.8
作者：
Chhabra, Preeti;de Graaf, Miranda;Vinje, Jan
通讯作者：
Vinje, Jan