Effect of sars-cov-2 proteins on vascular permeability

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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 vali-dating 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.

Original languageEnglish
Article numbere69314
JournaleLife
Volume10
DOIs
StatePublished - Oct 2021

Funding

FundersFunder number
10-1 Rami Nasser Avner Ehrlich Konstantinos Ioannidis Yaakov Nahmias Roded Sharan Yael Leichtmann-Bardoogo Ben Meir Maoz Yael Leichtmann-Bardoogo Ben Meir Maoz 3-17351 Rossana Rauti Yael Leichtmann-Bardoogo Ben Meir Maoz Uri Ashery Ben Meir Maoz Israel Science Foundation 953
16 Rina Tamir Victoria
Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease at Tel Aviv University
Parkinson's Disease Deutsche Forschungsgemeinschaft Teva Pharmaceutical Industries Zimin Ministry of Science and Technology, Israel TCCP Rossana Rauti Meishar Shahoha Yael Leichtmann-Bardoogo Eyal Paz Rina Tamir Victoria Miller Tal Babich Kfir Shaked Uri Ashery Ben Meir Maoz 207
TCCP953/16
Taube/Koret Global Collaboration in Neurodegenerative Diseases2417/20
Teva Pharmaceutical Industries
Horizon 2020 Framework Programme851765
European Research Council681870
Deutsche Forschungsgemeinschaft207/10–1
Israel Science Foundation2248/19
Azrieli Foundation
Ministry of Science and Technology, Israel3–17351

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