Zhu Yaohua, Wu Yan, Chai Yan, Qi Jianxun, Peng Ruchao, Feng Wen-Hai, Gao George Fu
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
J Virol. 2017 Dec 14;92(1). doi: 10.1128/JVI.01558-17. Print 2018 Jan 1.
(HRTV) is an emerging human pathogen that belongs to the newly defined family , order Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection. HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions. Here, we describe the crystal structure of HRTV Gc in its postfusion conformation. The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the family. However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, -linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation. This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses. Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens. HRTV is an insect-borne virus found in America that can infect humans. It belongs to the newly defined family , order HRTV contains three single-stranded RNA segments (L, M, and S). The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc. Gc is a fusion protein facilitating virus entry into host cells. Here, we report the crystal structure of the HRTV Gc protein. The structure displays a typical class II fusion protein conformation. Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses. Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations. This study provides useful information to improve protection against and therapies for bunyavirus infections.
（HRTV）是一种新兴的人类病原体，属于新定义的病毒科，目 Gn和Gc是由M节段编码的两种病毒表面糖蛋白，是感染早期事件所必需的。HRTV在低pH条件下通过病毒包膜与内体膜融合将其基因组传递到细胞质中。在此，我们描述了处于融合后构象的HRTV Gc的晶体结构。该结构表明Gc呈现典型的II类融合蛋白构象，并且整体结构与也属于该病毒科的严重发热伴血小板减少综合征病毒（SFTSV）Gc相同。然而，我们的结构分析表明，汉坦病毒Gc在亚结构域取向、连接糖基化、原体之间的相互作用模式以及融合环构象方面呈现出不同的特征。这表明它们在融合过程中具有家族特异性的亚基排列，并支持了最近对布尼亚病毒的分类学修订。我们的结果为两个布尼亚病毒科中II类膜融合蛋白的全面比较提供了见解，为针对这些人类病原体的治疗提供了有价值的信息。HRTV是一种在美洲发现的昆虫传播病毒，可感染人类。它属于新定义的病毒科，目 HRTV包含三个单链RNA节段（L、M和S）。该病毒的M节段编码一个多蛋白前体，该前体被切割成两种糖蛋白，Gn和Gc。Gc是一种促进病毒进入宿主细胞的融合蛋白。在此，我们报告了HRTV Gc蛋白的晶体结构。该结构呈现典型的II类融合蛋白构象。将HRTV Gc与另一种布尼亚病毒Gc最近解析的结构进行比较发现，这些Gc结构呈现出新定义的家族特异性，支持了最近国际病毒分类委员会对布尼亚病毒的重新分类。我们的结果扩展了对布尼亚病毒融合蛋白的认识，并帮助我们了解布尼亚病毒的特征。这项研究为改善针对布尼亚病毒感染的防护和治疗提供了有用的信息。
