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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...

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Autores principales: Wang, Zhaoqian, McCallum, Matthew, Yan, Lianying, Sharkey, William, Park, Young-Jun, Dang, Ha V., Amaya, Moushimi, Person, Ashley, Broder, Christopher C., Veesler, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
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.
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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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