| Autor: |
de Melo TC; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., Trevisan-Silva D; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., Alvarez-Flores MP; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., Gomes RN; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., de Souza MM; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., Valerio HP; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., Oliveira DS; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., DeOcesano-Pereira C; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil., Botosso VF; Virology Laboratory, Butantan Institute, São Paulo 05503900, Brazil., Calil Jorge SA; Viral Biotechnology Laboratory, Butantan Institute, São Paulo 05503900, Brazil., Schattner M; Laboratory of Experimental Thrombosis, Institute of Experimental Medicine (IMEX-CONICET-ANM), Buenos Aires 1425, Argentina., Gomez RM; Laboratory of Animal Viruses, Institute of Biotechnology and Molecular Biology, CONICET-UNLP, La Plata 1900, Argentina., Chudzinski-Tavassi AM; Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo 05503900, Brazil. |
| Abstrakt: |
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. |
