Structure and design of Langya virus glycoprotein antigens.
Structure and design of Langya virus glycoprotein antigens.
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琅琊病毒糖蛋白抗原的结构与设计。
DOI：
10.1101/2023.08.20.554025
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Veesler,David
中科院分区：
文献类型：
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作者：
Wang,Zhaoqian;McCallum,Matthew;Yan,Lianying;Sharkey,William;Park,Young-Jun;Dang,HaV;Amaya,Moushimi;Person,Ashley;Broder,ChristopherC;Veesler,David
狼牙病毒是从中国发热患者体内分离到的一种新近发现的黑热病病毒。HNV通过附着(G)和融合(F)糖蛋白进入宿主细胞，这是中和抗体的主要靶标。在这里，我们发现LayV F和G糖蛋白通过一种不同于Nipah病毒(NIV)和Hendra病毒(HEV)的未知受体来促进LayV F和G与人、小鼠和仓鼠靶细胞的膜融合，并且NIV和HEV诱导的单抗和多克隆抗体不与LayV F和G交叉反应。我们测定了LayV F、融合前和融合后以及LayV G的冷冻电子显微镜结构，揭示了它们相对于NIV和HEV的构象特征和明显的抗原性。我们通过计算设计了稳定化的LayV-G结构，并证明了HNV-F融合稳定化策略的普适性。我们的数据将支持针对LayV和密切相关的HNV的疫苗和疗法的开发。
Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse, and hamster target cells using a different, yet unknown, receptor than Nipah virus (NiV) and Hendra virus (HeV) and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryoelectron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing their conformational landscape and distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.