Effect of SARS-CoV-2 proteins on vascular permeability
| العنوان: | Effect of SARS-CoV-2 proteins on vascular permeability |
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| المؤلفون: | Yaakov Nahmias, Rami Nasser, Konstantinos Ioannidis, Rossana Rauti, Tal Babich, Avner Ehrlich, Victoria Miller, Meishar Shahoha, Eyal Paz, Yael Leichtmann-Bardoogo, Uri Ashery, Ben M. Maoz, Kfir Shaked, Rina Tamir, Roded Sharan |
| المصدر: | eLife eLife, Vol 10 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | CD31, vasculature, Endothelium, endothelium, QH301-705.5, Science, Vascular permeability, 030204 cardiovascular system & hematology, Biology, medicine.disease_cause, protein interactions, General Biochemistry, Genetics and Molecular Biology, Capillary Permeability, 03 medical and health sciences, Viral Proteins, 0302 clinical medicine, Von Willebrand factor, medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, Protein Interaction Maps, Endothelial dysfunction, Biology (General), 030304 developmental biology, Coronavirus, 0303 health sciences, Microbiology and Infectious Disease, Tight Junction Proteins, General Immunology and Microbiology, Tight junction, SARS-CoV-2, General Neuroscience, COVID-19, General Medicine, medicine.disease, 3. Good health, Cell biology, medicine.anatomical_structure, Host-Pathogen Interactions, biology.protein, Medicine, Endothelium, Vascular, Cytokine storm, Research Article, Human |
| الوصف: | 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. |
| تدمد: | 2050-084X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2c3f11da68fbddb20c8d89255cdae8f https://pubmed.ncbi.nlm.nih.gov/34694226 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d2c3f11da68fbddb20c8d89255cdae8f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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