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Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in se...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814814/ https://www.ncbi.nlm.nih.gov/pubmed/33469577 http://dx.doi.org/10.1101/2021.01.17.427024 |
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author | Andrews, Madeline G. Mukhtar, Tanzila Eze, Ugomma C. Simoneau, Camille R. Perez, Yonatan Mostajo-Radji, Mohammed A. Wang, Shaohui Velmeshev, Dmitry Salma, Jahan Kumar, G. Renuka Pollen, Alex A. Crouch, Elizabeth E. Ott, Melanie Kriegstein, Arnold R. |
author_facet | Andrews, Madeline G. Mukhtar, Tanzila Eze, Ugomma C. Simoneau, Camille R. Perez, Yonatan Mostajo-Radji, Mohammed A. Wang, Shaohui Velmeshev, Dmitry Salma, Jahan Kumar, G. Renuka Pollen, Alex A. Crouch, Elizabeth E. Ott, Melanie Kriegstein, Arnold R. |
author_sort | Andrews, Madeline G. |
collection | PubMed |
description | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in severity, accompany a significant proportion of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 and CD147. Inhibition of DPP4 reduced infection and decreased expression of the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for human astrocytes mediated by DPP4, resulting in reactive gliosis-type injury. |
format | Online Article Text |
id | pubmed-7814814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-78148142021-01-20 Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes Andrews, Madeline G. Mukhtar, Tanzila Eze, Ugomma C. Simoneau, Camille R. Perez, Yonatan Mostajo-Radji, Mohammed A. Wang, Shaohui Velmeshev, Dmitry Salma, Jahan Kumar, G. Renuka Pollen, Alex A. Crouch, Elizabeth E. Ott, Melanie Kriegstein, Arnold R. bioRxiv Article The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in severity, accompany a significant proportion of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 and CD147. Inhibition of DPP4 reduced infection and decreased expression of the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for human astrocytes mediated by DPP4, resulting in reactive gliosis-type injury. Cold Spring Harbor Laboratory 2021-01-18 /pmc/articles/PMC7814814/ /pubmed/33469577 http://dx.doi.org/10.1101/2021.01.17.427024 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Andrews, Madeline G. Mukhtar, Tanzila Eze, Ugomma C. Simoneau, Camille R. Perez, Yonatan Mostajo-Radji, Mohammed A. Wang, Shaohui Velmeshev, Dmitry Salma, Jahan Kumar, G. Renuka Pollen, Alex A. Crouch, Elizabeth E. Ott, Melanie Kriegstein, Arnold R. Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes |
title | Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes |
title_full | Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes |
title_fullStr | Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes |
title_full_unstemmed | Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes |
title_short | Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes |
title_sort | tropism of sars-cov-2 for developing human cortical astrocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814814/ https://www.ncbi.nlm.nih.gov/pubmed/33469577 http://dx.doi.org/10.1101/2021.01.17.427024 |
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