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Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes
Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of i...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132891/ https://www.ncbi.nlm.nih.gov/pubmed/35614127 http://dx.doi.org/10.1038/s41467-022-30658-0 |
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author | Wang, Chunyan Hesketh, Emma L. Shamorkina, Tatiana M. Li, Wentao Franken, Peter J. Drabek, Dubravka van Haperen, Rien Townend, Sarah van Kuppeveld, Frank J. M. Grosveld, Frank Ranson, Neil A. Snijder, Joost de Groot, Raoul J. Hurdiss, Daniel L. Bosch, Berend-Jan |
author_facet | Wang, Chunyan Hesketh, Emma L. Shamorkina, Tatiana M. Li, Wentao Franken, Peter J. Drabek, Dubravka van Haperen, Rien Townend, Sarah van Kuppeveld, Frank J. M. Grosveld, Frank Ranson, Neil A. Snijder, Joost de Groot, Raoul J. Hurdiss, Daniel L. Bosch, Berend-Jan |
author_sort | Wang, Chunyan |
collection | PubMed |
description | Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1(A) domain, but, remarkably, also to S1(B). The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1(B) epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2. |
format | Online Article Text |
id | pubmed-9132891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91328912022-05-27 Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes Wang, Chunyan Hesketh, Emma L. Shamorkina, Tatiana M. Li, Wentao Franken, Peter J. Drabek, Dubravka van Haperen, Rien Townend, Sarah van Kuppeveld, Frank J. M. Grosveld, Frank Ranson, Neil A. Snijder, Joost de Groot, Raoul J. Hurdiss, Daniel L. Bosch, Berend-Jan Nat Commun Article Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1(A) domain, but, remarkably, also to S1(B). The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1(B) epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2. Nature Publishing Group UK 2022-05-25 /pmc/articles/PMC9132891/ /pubmed/35614127 http://dx.doi.org/10.1038/s41467-022-30658-0 Text en © The Author(s) 2022 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 Wang, Chunyan Hesketh, Emma L. Shamorkina, Tatiana M. Li, Wentao Franken, Peter J. Drabek, Dubravka van Haperen, Rien Townend, Sarah van Kuppeveld, Frank J. M. Grosveld, Frank Ranson, Neil A. Snijder, Joost de Groot, Raoul J. Hurdiss, Daniel L. Bosch, Berend-Jan Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes |
title | Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes |
title_full | Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes |
title_fullStr | Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes |
title_full_unstemmed | Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes |
title_short | Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes |
title_sort | antigenic structure of the human coronavirus oc43 spike reveals exposed and occluded neutralizing epitopes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132891/ https://www.ncbi.nlm.nih.gov/pubmed/35614127 http://dx.doi.org/10.1038/s41467-022-30658-0 |
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