Environmentally-triggered contraction of the norovirus virion determines diarrheagenic potential.
Environmentally-triggered contraction of the norovirus virion determines diarrheagenic potential.
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DOI：
10.3389/fimmu.2022.1043746
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
诺如病毒是全世界严重儿童腹泻和食源性疾病的主要原因。虽然它们是所有年龄段的主要疾病原因，但幼儿的感染可能相当严重，每年估计有50,000-200,000名5岁以下儿童死亡。尽管人类感染诺沃克病毒造成了巨大的疾病负担，但人们对诺沃克病毒腹泻的致病机制知之甚少，主要是因为缺乏易于饲养的小动物模型。我们最近证实，野生型新生小鼠对小鼠诺如病毒(MNV)诱导的急性自决性腹泻的易感性与人类诺如病毒疾病的时间进程相一致。使用这个强大的致病模型系统，我们证明了毒力是由病毒衣壳对环境提示的反应性调节的，环境提示触发VP1突出(P)结构域到颗粒壳上的收缩，从而增强受体结合和感染性。给定MNV株经历这种收缩的能力与表达低丰度病毒受体CD300lf的细胞的感染呈正相关，支持一种模型，即病毒粒子收缩触发感染CD300lflo细胞类型，而CD300lflo细胞类型负责引起腹泻。这些发现直接将环境影响的生物物理特征与诺沃克病毒疾病的严重性联系起来。
Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course mirroring human norovirus disease. Using this robust pathogenesis model system, we demonstrate that virulence is regulated by the responsiveness of the viral capsid to environmental cues that trigger contraction of the VP1 protruding (P) domain onto the particle shell, thus enhancing receptor binding and infectivity. The capacity of a given MNV strain to undergo this contraction positively correlates with infection of cells expressing low abundance of the virus receptor CD300lf, supporting a model whereby virion contraction triggers infection of CD300lflo cell types that are responsible for diarrhea induction. These findings directly link environmentally-influenced biophysical features with norovirus disease severity.
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影响因子：
30.3
作者：
Lee S;Wilen CB;Orvedahl A;McCune BT;Kim KW;Orchard RC;Peterson ST;Nice TJ;Baldridge MT;Virgin HW
通讯作者：
Virgin HW
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：
56.9
作者：
Prasad, BVV;Hardy, ME;Estes, MK
通讯作者：
Estes, MK
影响因子：
3.8
作者：
Chhabra, Preeti;de Graaf, Miranda;Vinje, Jan
通讯作者：
Vinje, Jan
影响因子：
5.4
作者：
Graziano, Vincent R.;Alfajaro, Mia Madel;Wilen, Craig B.
通讯作者：
Wilen, Craig B.