Cryo-EM structure of severe fever with thrombocytopenia syndrome virus.
Cryo-EM structure of severe fever with thrombocytopenia syndrome virus.
复制标题
严重发热伴血小板减少综合征病毒的冷冻电镜结构。
DOI：
10.1038/s41467-023-41804-7
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发表时间：
2023-10-10
影响因子：
16.6
通讯作者：
Li, Chang
中科院分区：
文献类型：
--
作者：
Du, Shouwen;Peng, Ruchao;Xu, Wang;Qu, Xiaoyun;Wang, Yuhang;Wang, Jiamin;Li, Letian;Tian, Mingyao;Guan, Yudong;Wang, Jigang;Wang, Guoqing;Li, Hao;Deng, Lingcong;Shi, Xiaoshuang;Ma, Yidan;Liu, Fengting;Sun, Minhua;Wei, Zhengkai;Jin, Ningyi;Liu, Wei;Qi, Jianxun;Liu, Quan;Liao, Ming;Li, Chang
严重发热伴血小板减少综合征病毒（severe fever with thrombocytopenia syndrome virus，SFTSV）是一种由蜱传的人感染布尼亚病毒，它利用两种囊膜糖蛋白Gn和Gc进入宿主细胞。然而，这些糖蛋白在病毒体表面的结构和组织尚不清楚。在这里，我们描述的结构SFTSV确定的单粒子重建，这使得布尼亚病毒组装在近原子分辨率的机械见解。SFTSV Gn和Gc蛋白作为异二聚体存在，并进一步组装成五聚体和六聚体，通过异二聚体内和异二聚体间的相互作用屏蔽Gc融合环。单个peplomer主要通过胞外域缔合，其中Gc的N914上的高度保守聚糖起着至关重要的作用。这种精心设计的组装使Gc稳定在亚稳态融合前构象，并产生一些隐藏的表位，这些表位仅在病毒进入期间的中间状态下才可接近。这些发现为开发疫苗和治疗药物提供了重要依据。严重发热伴血小板减少综合征病毒（SFTSV，正式名称为大别带状疱疹病毒）是一种蜱传的人感染布尼亚病毒。本文报道了SFTSV病毒粒子的冷冻电镜结构，并讨论了病毒装配、膜融合和抗体中和的机制。
The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs. The severe fever with thrombocytopenia syndrome virus (SFTSV, officially named Dabie bandavirus) is a tick-borne human-infecting bunyavirus. Here, the authors report the cryo-EM structure of SFTSV virion, and discuss the mechanisms of viral assembly, membrane fusion and antibody neutralization.
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