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Structure and antigenicity of divergent Henipavirus fusion glycoproteins
In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275869/ https://www.ncbi.nlm.nih.gov/pubmed/37328468 http://dx.doi.org/10.1038/s41467-023-39278-8 |
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author | Isaacs, Ariel Low, Yu Shang Macauslane, Kyle L. Seitanidou, Joy Pegg, Cassandra L. Cheung, Stacey T. M. Liang, Benjamin Scott, Connor A. P. Landsberg, Michael J. Schulz, Benjamin L. Chappell, Keith J. Modhiran, Naphak Watterson, Daniel |
author_facet | Isaacs, Ariel Low, Yu Shang Macauslane, Kyle L. Seitanidou, Joy Pegg, Cassandra L. Cheung, Stacey T. M. Liang, Benjamin Scott, Connor A. P. Landsberg, Michael J. Schulz, Benjamin L. Chappell, Keith J. Modhiran, Naphak Watterson, Daniel |
author_sort | Isaacs, Ariel |
collection | PubMed |
description | In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs. |
format | Online Article Text |
id | pubmed-10275869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102758692023-06-18 Structure and antigenicity of divergent Henipavirus fusion glycoproteins Isaacs, Ariel Low, Yu Shang Macauslane, Kyle L. Seitanidou, Joy Pegg, Cassandra L. Cheung, Stacey T. M. Liang, Benjamin Scott, Connor A. P. Landsberg, Michael J. Schulz, Benjamin L. Chappell, Keith J. Modhiran, Naphak Watterson, Daniel Nat Commun Article In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs. Nature Publishing Group UK 2023-06-16 /pmc/articles/PMC10275869/ /pubmed/37328468 http://dx.doi.org/10.1038/s41467-023-39278-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Isaacs, Ariel Low, Yu Shang Macauslane, Kyle L. Seitanidou, Joy Pegg, Cassandra L. Cheung, Stacey T. M. Liang, Benjamin Scott, Connor A. P. Landsberg, Michael J. Schulz, Benjamin L. Chappell, Keith J. Modhiran, Naphak Watterson, Daniel Structure and antigenicity of divergent Henipavirus fusion glycoproteins |
title | Structure and antigenicity of divergent Henipavirus fusion glycoproteins |
title_full | Structure and antigenicity of divergent Henipavirus fusion glycoproteins |
title_fullStr | Structure and antigenicity of divergent Henipavirus fusion glycoproteins |
title_full_unstemmed | Structure and antigenicity of divergent Henipavirus fusion glycoproteins |
title_short | Structure and antigenicity of divergent Henipavirus fusion glycoproteins |
title_sort | structure and antigenicity of divergent henipavirus fusion glycoproteins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275869/ https://www.ncbi.nlm.nih.gov/pubmed/37328468 http://dx.doi.org/10.1038/s41467-023-39278-8 |
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