Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells

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de Melo, Thatiana Correa ; Trevisan-Silva, Dilza ; Alvarez-Flores, Miryam P. ; Gomes, Renata Nascimento ; de Souza, Marcelo Medina ; Valerio, Hellen Paula ; Oliveira, Douglas S. ; DeOcesano-Pereira, Carlos ; Botosso, Viviane Fongaro ; Calil Jorge, Soraia Attie ; Schattner, Mirta ; Gomez, Ricardo M. ; Chudzinski-Tavassi, Ana Marisa

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 18, p. 17-pg., 2022-09-01.

Resumo

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. (AU)

• Processo FAPESP: 20/10847-4 - Infecção por COVID-19 em modelos celulares humanos: busca por estratégias terapêuticas eficazes
• Beneficiário: Thatiana Corrêa de Melo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/05293-0 - Infecção por Coronavirus (SARS-Cov2) em modelos celulares humanos: busca por estratégias terapêuticas
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/13139-0 - Centro de Excelência na Descoberta de Novos Alvos
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia