Effect of SARS-CoV-2 proteins on vascular permeability

Severe acute respiratory syndrome (SARS)-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encode...

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Autores principales:	Rossana Rauti, Meishar Shahoha, Yael Leichtmann-Bardoogo, Rami Nasser, Eyal Paz, Rina Tamir, Victoria Miller, Tal Babich, Kfir Shaked, Avner Ehrlich, Konstantinos Ioannidis, Yaakov Nahmias, Roded Sharan, Uri Ashery, Ben Meir Maoz
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	SARS-COV-2 vasculature endothelium protein interactions Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2e26a1ded88e455da9a8f989c971aa4f
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spelling	oai:doaj.org-article:2e26a1ded88e455da9a8f989c971aa4f2021-11-26T11:14:18ZEffect of SARS-CoV-2 proteins on vascular permeability10.7554/eLife.693142050-084Xe69314https://doaj.org/article/2e26a1ded88e455da9a8f989c971aa4f2021-10-01T00:00:00Zhttps://elifesciences.org/articles/69314https://doaj.org/toc/2050-084XSevere acute respiratory syndrome (SARS)-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2, nsp5_c145a (catalytic dead mutant of nsp5), and nsp7 also reduced CD31, and increased von Willebrand factor expression and IL-6, suggesting endothelial dysfunction. Using propagation-based analysis of a protein–protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS-CoV-2 protein in other tissues affected by coronavirus disease (COVID-19). While validating the PPI network model, we found that the tight junction (TJ) proteins cadherin-5, ZO-1, and β-catenin are affected by nsp2, nsp5_c145a, and nsp7 consistent with the model prediction. Overall, this work identifies the SARS-CoV-2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID-19.Rossana RautiMeishar ShahohaYael Leichtmann-BardoogoRami NasserEyal PazRina TamirVictoria MillerTal BabichKfir ShakedAvner EhrlichKonstantinos IoannidisYaakov NahmiasRoded SharanUri AsheryBen Meir MaozeLife Sciences Publications LtdarticleSARS-COV-2vasculatureendotheliumprotein interactionsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-COV-2 vasculature endothelium protein interactions Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	SARS-COV-2 vasculature endothelium protein interactions Medicine R Science Q Biology (General) QH301-705.5 Rossana Rauti Meishar Shahoha Yael Leichtmann-Bardoogo Rami Nasser Eyal Paz Rina Tamir Victoria Miller Tal Babich Kfir Shaked Avner Ehrlich Konstantinos Ioannidis Yaakov Nahmias Roded Sharan Uri Ashery Ben Meir Maoz Effect of SARS-CoV-2 proteins on vascular permeability
description	Severe acute respiratory syndrome (SARS)-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2, nsp5_c145a (catalytic dead mutant of nsp5), and nsp7 also reduced CD31, and increased von Willebrand factor expression and IL-6, suggesting endothelial dysfunction. Using propagation-based analysis of a protein–protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS-CoV-2 protein in other tissues affected by coronavirus disease (COVID-19). While validating the PPI network model, we found that the tight junction (TJ) proteins cadherin-5, ZO-1, and β-catenin are affected by nsp2, nsp5_c145a, and nsp7 consistent with the model prediction. Overall, this work identifies the SARS-CoV-2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID-19.
format	article
author	Rossana Rauti Meishar Shahoha Yael Leichtmann-Bardoogo Rami Nasser Eyal Paz Rina Tamir Victoria Miller Tal Babich Kfir Shaked Avner Ehrlich Konstantinos Ioannidis Yaakov Nahmias Roded Sharan Uri Ashery Ben Meir Maoz
author_facet	Rossana Rauti Meishar Shahoha Yael Leichtmann-Bardoogo Rami Nasser Eyal Paz Rina Tamir Victoria Miller Tal Babich Kfir Shaked Avner Ehrlich Konstantinos Ioannidis Yaakov Nahmias Roded Sharan Uri Ashery Ben Meir Maoz
author_sort	Rossana Rauti
title	Effect of SARS-CoV-2 proteins on vascular permeability
title_short	Effect of SARS-CoV-2 proteins on vascular permeability
title_full	Effect of SARS-CoV-2 proteins on vascular permeability
title_fullStr	Effect of SARS-CoV-2 proteins on vascular permeability
title_full_unstemmed	Effect of SARS-CoV-2 proteins on vascular permeability
title_sort	effect of sars-cov-2 proteins on vascular permeability
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/2e26a1ded88e455da9a8f989c971aa4f
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_version_	1718409525922365440

Effect of SARS-CoV-2 proteins on vascular permeability

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