Imperial College London
Alternate

DrGraemeBirdsey

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer in Vascular Science
 
 
 
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Contact

 

+44 (0)20 7594 8633g.birdsey Website

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{McCracken:2022:10.1101/2020.12.02.391664,
author = {McCracken, I and Saginc, G and He, L and Huseynov, A and Daniels, A and Fletcher, S and Peghaire, C and Kalna, V and Andaloussi-Mäe, M and Muhl, L and Craig, NM and Griffiths, SJ and Haas, JG and Tait-Burkard, C and Lendahl, U and Birdsey, GM and Betsholtz, C and Noseda, M and Baker, A and Randi, AM},
doi = {10.1101/2020.12.02.391664},
publisher = {Cold Spring Harbor Laboratory},
title = {Lack of evidence of ACE2 expression and replicative infection by SARS-CoV-2 in human endothelial cells},
url = {http://dx.doi.org/10.1101/2020.12.02.391664},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Abstract: A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating human bulk and single-cell transcriptomic data, we found <jats:italic>ACE2</jats:italic> expression in endothelial cells to be extremely low or absent <jats:italic>in vivo</jats:italic> and not upregulated by exposure to inflammatory agents <jats:italic>in vitro</jats:italic>. Also, the endothelial chromatin landscape at the <jats:italic>ACE2</jats:italic> locus showed presence of repressive and absence of activation marks, suggesting that the gene is inactive in endothelial cells. Finally, we failed to achieve infection and replication of SARS-CoV-2 in cultured human endothelial cells, which were permissive to productive infection by coronavirus 229E that uses CD13 as the receptor. Our data suggest that SARS-Cov-2 is unlikely to infect endothelial cells directly; these findings are consistent with a scenario where endothelial injury is indirectly caused by the infection of neighbouring epithelial cells and/or due to systemic effects mediated by immune cells, platelets, complement activation, and/or proinflammatory cytokines
AU  - McCracken,I
AU  - Saginc,G
AU  - He,L
AU  - Huseynov,A
AU  - Daniels,A
AU  - Fletcher,S
AU  - Peghaire,C
AU  - Kalna,V
AU  - Andaloussi-Mäe,M
AU  - Muhl,L
AU  - Craig,NM
AU  - Griffiths,SJ
AU  - Haas,JG
AU  - Tait-Burkard,C
AU  - Lendahl,U
AU  - Birdsey,GM
AU  - Betsholtz,C
AU  - Noseda,M
AU  - Baker,A
AU  - Randi,AM
DO  - 10.1101/2020.12.02.391664
PB  - Cold Spring Harbor Laboratory
PY  - 2022///
TI  - Lack of evidence of ACE2 expression and replicative infection by SARS-CoV-2 in human endothelial cells
UR  - http://dx.doi.org/10.1101/2020.12.02.391664
UR  - https://www.biorxiv.org/content/10.1101/2020.12.02.391664v1
UR  - http://hdl.handle.net/10044/1/98346
ER  -
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