Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10452 |
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| author | Thatiana Corrêa de Melo Dilza Trevisan-Silva Miryam P. Alvarez-Flores Renata Nascimento Gomes Marcelo Medina de Souza Hellen Paula Valerio Douglas S. Oliveira Carlos DeOcesano-Pereira Viviane Fongaro Botosso Soraia Attie Calil Jorge Mirta Schattner Ricardo M. Gomez Ana Marisa Chudzinski-Tavassi |
| author_facet | Thatiana Corrêa de Melo Dilza Trevisan-Silva Miryam P. Alvarez-Flores Renata Nascimento Gomes Marcelo Medina de Souza Hellen Paula Valerio Douglas S. Oliveira Carlos DeOcesano-Pereira Viviane Fongaro Botosso Soraia Attie Calil Jorge Mirta Schattner Ricardo M. Gomez Ana Marisa Chudzinski-Tavassi |
| author_sort | Thatiana Corrêa de Melo |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction. |
| first_indexed | 2024-03-09T23:46:51Z |
| format | Article |
| id | doaj.art-85308536820c4380b3da93748640aac2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:51Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-85308536820c4380b3da93748640aac22023-11-23T16:41:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181045210.3390/ijms231810452Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial CellsThatiana Corrêa de Melo0Dilza Trevisan-Silva1Miryam P. Alvarez-Flores2Renata Nascimento Gomes3Marcelo Medina de Souza4Hellen Paula Valerio5Douglas S. Oliveira6Carlos DeOcesano-Pereira7Viviane Fongaro Botosso8Soraia Attie Calil Jorge9Mirta Schattner10Ricardo M. Gomez11Ana Marisa Chudzinski-Tavassi12Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilVirology Laboratory, Butantan Institute, São Paulo 05503900, BrazilViral Biotechnology Laboratory, Butantan Institute, São Paulo 05503900, BrazilLaboratory of Experimental Thrombosis, Institute of Experimental Medicine (IMEX-CONICET-ANM), Buenos Aires 1425, ArgentinaLaboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CONICET-UNLP, La Plata 1900, ArgentinaCentre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, BrazilSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction.https://www.mdpi.com/1422-0067/23/18/10452SARS-CoV-2endothelial cellsproteomicsmass spectrometryHUVECs |
| spellingShingle | Thatiana Corrêa de Melo Dilza Trevisan-Silva Miryam P. Alvarez-Flores Renata Nascimento Gomes Marcelo Medina de Souza Hellen Paula Valerio Douglas S. Oliveira Carlos DeOcesano-Pereira Viviane Fongaro Botosso Soraia Attie Calil Jorge Mirta Schattner Ricardo M. Gomez Ana Marisa Chudzinski-Tavassi Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells International Journal of Molecular Sciences SARS-CoV-2 endothelial cells proteomics mass spectrometry HUVECs |
| title | Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells |
| title_full | Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells |
| title_fullStr | Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells |
| title_full_unstemmed | Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells |
| title_short | Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells |
| title_sort | proteomic analysis identifies molecular players and biological processes specific to sars cov 2 exposure in endothelial cells |
| topic | SARS-CoV-2 endothelial cells proteomics mass spectrometry HUVECs |
| url | https://www.mdpi.com/1422-0067/23/18/10452 |
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