Antigenic and structural insights into Langya henipavirus attachment glycoprotein

Yaohui Li; Xiaoyan Huang; Xiaodong Zai; Chenfeng Mao; Ruihua Li; Yamei Feng; Yue Zhang; Zhang Zhang; Jun Zhang; Junjie Xu

doi:10.1016/j.virs.2025.08.005

October 2025

Citation: Yaohui Li, Xiaoyan Huang, Xiaodong Zai, Chenfeng Mao, Ruihua Li, Yamei Feng, Yue Zhang, Zhang Zhang, Jun Zhang, Junjie Xu. Antigenic and structural insights into Langya henipavirus attachment glycoprotein .VIROLOGICA SINICA, 2025, 40(5) : 769-777. http://dx.doi.org/10.1016/j.virs.2025.08.005

Antigenic and structural insights into Langya henipavirus attachment glycoprotein

Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, 100071, China

Corresponding author: Junjie Xu, xujunjie@sina.com
Received Date: 31 December 2024
Accepted Date: 29 August 2025
Available online: 02 September 2025

Abstract

The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment (G) and fusion (F) glycoproteins with receptors on the cell surface. Langya henipavirus (LayV) was newly identified in China in 2022. The G proteins of LayV and Mojiang virus (MojV) exhibit high amino acid homology (86%), while they are located in a unique evolutionary clade within the Henipavirus genus. In this study, the crystal structure of the LayV G protein was resolved at a 3.37 Å resolution, revealing a head domain with six β-propeller-like domains distinct from other henipavirus G proteins, such as those of Nipah virus (NiV) and Hendra virus (HeV). Furthermore, the prominent loop in the center cavity of the LayV G protein showed unique structural features. In the ELISA and SPR assays, the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor. Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein. These antibodies exhibited strong reactivity against both LayV and MojV G proteins. However, only weak cross-reactivity was observed with other henipaviruses. Moreover, eight monoclonal antibodies targeting the LayV G protein were generated, two of which exhibited broad binding activity across different henipavirus G proteins. These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses
- Langya henipavirus (LayV)
- , Attachment glycoprotein
- , Crystal structure
- , Glycosylation
- , Immunogenicity
- , Monoclonal antibodies

Electronic Supplementary Material

10.1016j.virs.2025.08.005-ESM1.docx
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