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Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit di...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875398/ https://www.ncbi.nlm.nih.gov/pubmed/33513210 http://dx.doi.org/10.1371/journal.ppat.1009287 |
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author | Graham, Jessica B. Swarts, Jessica L. Leist, Sarah R. Schäfer, Alexandra Menachery, Vineet D. Gralinski, Lisa E. Jeng, Sophia Miller, Darla R. Mooney, Michael A. McWeeney, Shannon K. Ferris, Martin T. Pardo-Manuel de Villena, Fernando Heise, Mark T. Baric, Ralph S. Lund, Jennifer M. |
author_facet | Graham, Jessica B. Swarts, Jessica L. Leist, Sarah R. Schäfer, Alexandra Menachery, Vineet D. Gralinski, Lisa E. Jeng, Sophia Miller, Darla R. Mooney, Michael A. McWeeney, Shannon K. Ferris, Martin T. Pardo-Manuel de Villena, Fernando Heise, Mark T. Baric, Ralph S. Lund, Jennifer M. |
author_sort | Graham, Jessica B. |
collection | PubMed |
description | The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease. |
format | Online Article Text |
id | pubmed-7875398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78753982021-02-19 Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice Graham, Jessica B. Swarts, Jessica L. Leist, Sarah R. Schäfer, Alexandra Menachery, Vineet D. Gralinski, Lisa E. Jeng, Sophia Miller, Darla R. Mooney, Michael A. McWeeney, Shannon K. Ferris, Martin T. Pardo-Manuel de Villena, Fernando Heise, Mark T. Baric, Ralph S. Lund, Jennifer M. PLoS Pathog Research Article The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease. Public Library of Science 2021-01-29 /pmc/articles/PMC7875398/ /pubmed/33513210 http://dx.doi.org/10.1371/journal.ppat.1009287 Text en © 2021 Graham et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Graham, Jessica B. Swarts, Jessica L. Leist, Sarah R. Schäfer, Alexandra Menachery, Vineet D. Gralinski, Lisa E. Jeng, Sophia Miller, Darla R. Mooney, Michael A. McWeeney, Shannon K. Ferris, Martin T. Pardo-Manuel de Villena, Fernando Heise, Mark T. Baric, Ralph S. Lund, Jennifer M. Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice |
title | Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice |
title_full | Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice |
title_fullStr | Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice |
title_full_unstemmed | Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice |
title_short | Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice |
title_sort | baseline t cell immune phenotypes predict virologic and disease control upon sars-cov infection in collaborative cross mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875398/ https://www.ncbi.nlm.nih.gov/pubmed/33513210 http://dx.doi.org/10.1371/journal.ppat.1009287 |
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