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Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity
SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2–infected cells or N-expressing transfected cells binds to neighboring cells by electro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348789/ https://www.ncbi.nlm.nih.gov/pubmed/35921414 http://dx.doi.org/10.1126/sciadv.abp9770 |
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author | López-Muñoz, Alberto Domingo Kosik, Ivan Holly, Jaroslav Yewdell, Jonathan W. |
author_facet | López-Muñoz, Alberto Domingo Kosik, Ivan Holly, Jaroslav Yewdell, Jonathan W. |
author_sort | López-Muñoz, Alberto Domingo |
collection | PubMed |
description | SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2–infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Anti-N Abs bound to the surface of N-expressing cells activate Fc receptor–expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc-expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains. |
format | Online Article Text |
id | pubmed-9348789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-93487892022-08-18 Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity López-Muñoz, Alberto Domingo Kosik, Ivan Holly, Jaroslav Yewdell, Jonathan W. Sci Adv Biomedicine and Life Sciences SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2–infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Anti-N Abs bound to the surface of N-expressing cells activate Fc receptor–expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc-expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains. American Association for the Advancement of Science 2022-08-03 /pmc/articles/PMC9348789/ /pubmed/35921414 http://dx.doi.org/10.1126/sciadv.abp9770 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences López-Muñoz, Alberto Domingo Kosik, Ivan Holly, Jaroslav Yewdell, Jonathan W. Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity |
title | Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity |
title_full | Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity |
title_fullStr | Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity |
title_full_unstemmed | Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity |
title_short | Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity |
title_sort | cell surface sars-cov-2 nucleocapsid protein modulates innate and adaptive immunity |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348789/ https://www.ncbi.nlm.nih.gov/pubmed/35921414 http://dx.doi.org/10.1126/sciadv.abp9770 |
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