Chikungunya virus assembly and budding visualized in situ using cryogenic electron tomography.
Chikungunya virus assembly and budding visualized in situ using cryogenic electron tomography.
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DOI：
10.1038/s41564-022-01164-2
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发表时间：
2022-08
影响因子：
28.3
通讯作者：
中科院分区：
文献类型：
--
作者：
基孔肯雅病毒（CHIKV）是一种代表性的甲病毒，可引起人类衰弱性关节炎疾病。甲病毒颗粒组装成两个二十面体层：包埋在脂质包膜中的糖蛋白刺突壳和内部核衣壳（NC）核心。与一些包膜病毒的基质驱动组装相反，双层二十面体颗粒的组装/出芽过程仍然知之甚少。在这里，我们使用低温电子断层扫描（cryoET）来捕获受感染的人类细胞中CHIKV组装的快照。子体积分类的快照显示12个中间体，代表不同阶段的组装在质膜。从亚纳米到纳米分辨率范围内的进一步亚断层平均结构显示，不成熟的非二十面体NC作为粗糙的支架来触发尖峰晶格的二十面体组装，这反过来又在出芽过程中逐渐将底层NC转化为二十面体核心。此外，对用出芽抑制抗体处理的CHIKV感染的细胞的分析显示，棘突之间的空间比二十面体棘突晶格中的更宽，这表明将棘突间隔开以防止它们的横向相互作用防止了NC周围的质膜弯曲，从而阻断了病毒出芽。这些发现提供了甲病毒组装和抗体介导的出芽抑制的分子机制，这为开发靶向二十面体包膜病毒组装的广泛治疗剂提供了有价值的见解。
Chikungunya virus (CHIKV) is a representative alphavirus causing debilitating arthritogenic disease in humans. Alphavirus particles assemble into two icosahedral layers: the glycoprotein spike shell embedded in a lipid envelope and the inner nucleocapsid (NC) core. In contrast to matrix-driven assembly of some enveloped viruses, the assembly/budding process of two-layered icosahedral particles remains poorly understood. Here we used cryogenic electron tomography (cryoET) to capture snapshots of the CHIKV assembly in infected human cells. Subvolume classification of the snapshots revealed 12 intermediates, representing different stages of assembly at the plasma membrane. Further subtomogram average structures ranging from subnanometer to nanometer resolutions show that immature, non-icosahedral NCs function as rough scaffolds to trigger icosahedral assembly of the spike lattice, which in turn progressively transforms the underlying NCs into icosahedral cores during budding. Further, analysis of CHIKV-infected cells treated with budding-inhibiting antibodies revealed wider spaces between spikes than in icosahedral spike lattice, suggesting that spacing spikes apart to prevent their lateral interactions prevents the plasma membrane bending around NC, thus blocking virus budding. These findings provide the molecular mechanisms for alphavirus assembly and antibody mediated budding inhibition that provide valuable insights in development of broad therapeutics targeting assembly of icosahedral enveloped viruses.
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影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
30.3
作者：
Jin J;Galaz-Montoya JG;Sherman MB;Sun SY;Goldsmith CS;O'Toole ET;Ackerman L;Carlson LA;Weaver SC;Chiu W;Simmons G
通讯作者：
Simmons G
DOI：
10.1016/b978-0-12-814515-9.00023-0
发表时间：
2021-03-01
期刊：
Encyclopedia of Virology
影响因子：
--
作者：
Rheinemann L;Sundquist WI
通讯作者：
Sundquist WI
影响因子：
64.5
作者：
Kim AS;Kafai NM;Winkler ES;Gilliland TC Jr;Cottle EL;Earnest JT;Jethva PN;Kaplonek P;Shah AP;Fong RH;Davidson E;Malonis RJ;Quiroz JA;Williamson LE;Vang L;Mack M;Crowe JE Jr;Doranz BJ;Lai JR;Alter G;Gross ML;Klimstra WB;Fremont DH;Diamond MS
通讯作者：
Diamond MS
影响因子：
6.7
作者：
Martinez MG;Kielian M
通讯作者：
Kielian M