Cargando…
Dissecting human population variation in single-cell responses to SARS-CoV-2
Humans display substantial interindividual clinical variability after SARS-CoV-2 infection(1–3), the genetic and immunological basis of which has begun to be deciphered(4). However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report sing...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482701/ https://www.ncbi.nlm.nih.gov/pubmed/37558883 http://dx.doi.org/10.1038/s41586-023-06422-9 |
_version_ | 1785102230117941248 |
---|---|
author | Aquino, Yann Bisiaux, Aurélie Li, Zhi O’Neill, Mary Mendoza-Revilla, Javier Merkling, Sarah Hélène Kerner, Gaspard Hasan, Milena Libri, Valentina Bondet, Vincent Smith, Nikaïa de Cevins, Camille Ménager, Mickaël Luca, Francesca Pique-Regi, Roger Barba-Spaeth, Giovanna Pietropaoli, Stefano Schwartz, Olivier Leroux-Roels, Geert Lee, Cheuk-Kwong Leung, Kathy Wu, Joseph T. Peiris, Malik Bruzzone, Roberto Abel, Laurent Casanova, Jean-Laurent Valkenburg, Sophie A. Duffy, Darragh Patin, Etienne Rotival, Maxime Quintana-Murci, Lluis |
author_facet | Aquino, Yann Bisiaux, Aurélie Li, Zhi O’Neill, Mary Mendoza-Revilla, Javier Merkling, Sarah Hélène Kerner, Gaspard Hasan, Milena Libri, Valentina Bondet, Vincent Smith, Nikaïa de Cevins, Camille Ménager, Mickaël Luca, Francesca Pique-Regi, Roger Barba-Spaeth, Giovanna Pietropaoli, Stefano Schwartz, Olivier Leroux-Roels, Geert Lee, Cheuk-Kwong Leung, Kathy Wu, Joseph T. Peiris, Malik Bruzzone, Roberto Abel, Laurent Casanova, Jean-Laurent Valkenburg, Sophie A. Duffy, Darragh Patin, Etienne Rotival, Maxime Quintana-Murci, Lluis |
author_sort | Aquino, Yann |
collection | PubMed |
description | Humans display substantial interindividual clinical variability after SARS-CoV-2 infection(1–3), the genetic and immunological basis of which has begun to be deciphered(4). However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells—from 222 healthy donors of diverse ancestries—that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk. |
format | Online Article Text |
id | pubmed-10482701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104827012023-09-08 Dissecting human population variation in single-cell responses to SARS-CoV-2 Aquino, Yann Bisiaux, Aurélie Li, Zhi O’Neill, Mary Mendoza-Revilla, Javier Merkling, Sarah Hélène Kerner, Gaspard Hasan, Milena Libri, Valentina Bondet, Vincent Smith, Nikaïa de Cevins, Camille Ménager, Mickaël Luca, Francesca Pique-Regi, Roger Barba-Spaeth, Giovanna Pietropaoli, Stefano Schwartz, Olivier Leroux-Roels, Geert Lee, Cheuk-Kwong Leung, Kathy Wu, Joseph T. Peiris, Malik Bruzzone, Roberto Abel, Laurent Casanova, Jean-Laurent Valkenburg, Sophie A. Duffy, Darragh Patin, Etienne Rotival, Maxime Quintana-Murci, Lluis Nature Article Humans display substantial interindividual clinical variability after SARS-CoV-2 infection(1–3), the genetic and immunological basis of which has begun to be deciphered(4). However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells—from 222 healthy donors of diverse ancestries—that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk. Nature Publishing Group UK 2023-08-09 2023 /pmc/articles/PMC10482701/ /pubmed/37558883 http://dx.doi.org/10.1038/s41586-023-06422-9 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Aquino, Yann Bisiaux, Aurélie Li, Zhi O’Neill, Mary Mendoza-Revilla, Javier Merkling, Sarah Hélène Kerner, Gaspard Hasan, Milena Libri, Valentina Bondet, Vincent Smith, Nikaïa de Cevins, Camille Ménager, Mickaël Luca, Francesca Pique-Regi, Roger Barba-Spaeth, Giovanna Pietropaoli, Stefano Schwartz, Olivier Leroux-Roels, Geert Lee, Cheuk-Kwong Leung, Kathy Wu, Joseph T. Peiris, Malik Bruzzone, Roberto Abel, Laurent Casanova, Jean-Laurent Valkenburg, Sophie A. Duffy, Darragh Patin, Etienne Rotival, Maxime Quintana-Murci, Lluis Dissecting human population variation in single-cell responses to SARS-CoV-2 |
title | Dissecting human population variation in single-cell responses to SARS-CoV-2 |
title_full | Dissecting human population variation in single-cell responses to SARS-CoV-2 |
title_fullStr | Dissecting human population variation in single-cell responses to SARS-CoV-2 |
title_full_unstemmed | Dissecting human population variation in single-cell responses to SARS-CoV-2 |
title_short | Dissecting human population variation in single-cell responses to SARS-CoV-2 |
title_sort | dissecting human population variation in single-cell responses to sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482701/ https://www.ncbi.nlm.nih.gov/pubmed/37558883 http://dx.doi.org/10.1038/s41586-023-06422-9 |
work_keys_str_mv | AT aquinoyann dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT bisiauxaurelie dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT lizhi dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT oneillmary dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT mendozarevillajavier dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT merklingsarahhelene dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT kernergaspard dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT hasanmilena dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT librivalentina dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT bondetvincent dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT smithnikaia dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT decevinscamille dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT menagermickael dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT lucafrancesca dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT piqueregiroger dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT barbaspaethgiovanna dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT pietropaolistefano dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT schwartzolivier dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT lerouxroelsgeert dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT leecheukkwong dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT leungkathy dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT wujosepht dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT peirismalik dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT bruzzoneroberto dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT abellaurent dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT casanovajeanlaurent dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT valkenburgsophiea dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT duffydarragh dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT patinetienne dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT rotivalmaxime dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 AT quintanamurcilluis dissectinghumanpopulationvariationinsinglecellresponsestosarscov2 |