Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7564-E7573. doi: 10.1073/pnas.1705176114. Epub 2017 Aug 21.
Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4-5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.
严重发热伴血小板减少综合征病毒（SFTSV）和裂谷热病毒（RVFV）是两种虫媒黄病毒科病毒，可引起人类和动物的严重疾病。糖蛋白 N（Gn）是病毒表面的一种包膜蛋白，是主要的抗原成分。尽管它对于病毒进入和融合很重要，但黄病毒 Gn 的分子特征尚不清楚。在这里，我们展示了 SFTSV 和 RVFV 的 Gn 头部结构域的晶体结构，它们整体上呈现出相似的紧凑三角形形状，而构成 Gn 头部的三个亚结构域（I、II 和 III 结构域）则呈现出不同的排列。Gn 茎区的 10 个半胱氨酸在黄病毒中保守，其中 4 个负责 Gn 二聚化，正如本研究所揭示的，它们在所有成员中高度保守。因此，我们提出了一种在病毒表面的锚定模式。SFTSV Gn 头部和人类中和抗体 MAb 4-5 的复合物结构表明，III 结构域中的α6 螺旋是中和的关键组成部分。重要的是，该结构表明 III 结构域是被特定中和抗体识别的理想区域，而 II 结构域可能被广泛中和抗体识别。总的来说，Gn 是一种理想的疫苗靶标，我们的数据为针对黄病毒引起的疾病的疫苗的合理设计提供了分子基础，并为 bunyavirus Gn 在病毒表面的嵌入提供了模型。
