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Structure and design of Langya virus glycoprotein antigens
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 pr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462157/ https://www.ncbi.nlm.nih.gov/pubmed/37645760 http://dx.doi.org/10.1101/2023.08.20.554025 |
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author | Wang, Zhaoqian McCallum, Matthew Yan, Lianying Sharkey, William Park, Young-Jun Dang, Ha V. Amaya, Moushimi Person, Ashley Broder, Christopher C. Veesler, David |
author_facet | Wang, Zhaoqian McCallum, Matthew Yan, Lianying Sharkey, William Park, Young-Jun Dang, Ha V. Amaya, Moushimi Person, Ashley Broder, Christopher C. Veesler, David |
author_sort | Wang, Zhaoqian |
collection | PubMed |
description | 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 NiV and HeV and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryo-electron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing previously unknown conformational landscapes and their 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. |
format | Online Article Text |
id | pubmed-10462157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104621572023-08-29 Structure and design of Langya virus glycoprotein antigens Wang, Zhaoqian McCallum, Matthew Yan, Lianying Sharkey, William Park, Young-Jun Dang, Ha V. Amaya, Moushimi Person, Ashley Broder, Christopher C. Veesler, David bioRxiv Article 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 NiV and HeV and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryo-electron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing previously unknown conformational landscapes and their 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. Cold Spring Harbor Laboratory 2023-08-26 /pmc/articles/PMC10462157/ /pubmed/37645760 http://dx.doi.org/10.1101/2023.08.20.554025 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Wang, Zhaoqian McCallum, Matthew Yan, Lianying Sharkey, William Park, Young-Jun Dang, Ha V. Amaya, Moushimi Person, Ashley Broder, Christopher C. Veesler, David Structure and design of Langya virus glycoprotein antigens |
title | Structure and design of Langya virus glycoprotein antigens |
title_full | Structure and design of Langya virus glycoprotein antigens |
title_fullStr | Structure and design of Langya virus glycoprotein antigens |
title_full_unstemmed | Structure and design of Langya virus glycoprotein antigens |
title_short | Structure and design of Langya virus glycoprotein antigens |
title_sort | structure and design of langya virus glycoprotein antigens |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462157/ https://www.ncbi.nlm.nih.gov/pubmed/37645760 http://dx.doi.org/10.1101/2023.08.20.554025 |
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