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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...

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Autores principales: López-Muñoz, Alberto Domingo, Kosik, Ivan, Holly, Jaroslav, Yewdell, Jonathan W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
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.
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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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