Structure and function of a pair of non-competing monoclonal antibodies against Langya henipavirus attachment glycoprotein.

IF 6.9 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-10-09 DOI:10.1016/j.celrep.2025.116407

Wenting Li, Songyue Wu, Qi Gui, Congcong Liu, Bing Zhou, Hu Yan, Yuehong Sun, Qing Fan, Yuzheng Zhou, Huimin Guo, Shilong Tang, Xiangyang Ge, Bin Ju, Renhong Yan, Zheng Zhang

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Abstract

Langya henipavirus (LayV) is a zoonotic Parahenipavirus (Para-HNV) identified in recent years, discovered via surveillance of febrile patients with recent animal exposure in eastern China. The attachment glycoprotein (G) of HNV is critical for host cell entry and a key immune target. However, LayV-G exhibits notable antigenic differences from G of highly pathogenic bat-borne Hendra virus (HEV) and Nipah virus (NiV), implying vaccines or antibody therapies developed against HeV/NiV-G might be ineffective against LayV. Here, we immunize mice with LayV-G ectodomain and isolate a panel of LayV-G-targeting monoclonal antibodies (mAbs). We characterize two potent mAbs with pronounced crystallizable fragment (Fc)-mediated antiviral function and determine their cryo-electron microscopy (cryo-EM) structure binding to distinct epitopes of LayV-G head domain at a resolution of 2.92 Å, revealing antibody recognition mechanisms and potential conformational dynamics of LayV-G. Overall, our study defines two function-related epitopes of LayV-G, laying the foundation for therapeutic antibody development and vaccine design.

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一对抗狼牙亨尼帕病毒附着糖蛋白的非竞争单克隆抗体的结构和功能。

琅琊尼帕病毒（LayV）是近年来在中国东部对近期与动物接触的发热患者进行监测时发现的一种人畜共患的旁尼帕病毒（Para-HNV）。乙型肝炎病毒的附着糖蛋白（attachment glycoprotein， G）是进入宿主细胞的关键蛋白，也是重要的免疫靶点。然而，LayV-G与高致病性亨德拉病毒（HEV）和尼帕病毒（NiV）的G表现出显著的抗原差异，这意味着针对HEV /NiV-G的疫苗或抗体疗法可能对LayV无效。在这里，我们用LayV-G外结构域免疫小鼠，并分离出一组LayV-G靶向单克隆抗体（mab）。我们鉴定了两种具有明显的可结晶片段（Fc）介导抗病毒功能的有效单克隆抗体，并以2.92 Å的分辨率测定了它们与LayV-G头部结构域不同表位结合的低温电镜（cryo-EM）结构，揭示了LayV-G的抗体识别机制和潜在的构象动力学。总的来说，我们的研究确定了LayV-G的两个功能相关的表位，为治疗性抗体的开发和疫苗设计奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.