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

Abstract

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.

Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

“…4A). However, in line with previous evidence [33][34][35][36], in all the experimental conditions we failed to detect viral proteins at intracellular level (Fig. 4B).…”

“…Next, we sought to investigate whether the impaired α-syn multimerization observed in virus-susceptible epithelial cells occurs also in experimental models featuring non-productive SARS-CoV-2 infection. To such an aim, human endothelial umbilical vein cells (HUVECs) were used, as they have been widely documented to express very low levels of the SARS-CoV-2 receptor ACE2 and the protease TMPRSS2, which restrains their capacity for productive viral infection [33][34][35][36]. Initial results showed a time-related increase in SARS-CoV-2 N gene mRNA expression in HUVECs supernatants (Fig.…”

Prothymosin α accelerates dengue virus-induced thrombocytopenia

“…In human umbilical vein endothelial cells (HUVECs), ProT is overexpressed under hypoxic conditions 43 or after viral infection. 44 Interactions of endothelial cells and PLTs are important for developing dengue complications. Thus, overexpression of ProT in endothelial cells may contribute not only to increased PLT clearance, thereby reducing PLT numbers, but also to extended bleeding times in ProT Tg mice.…”

The D405N Mutation in the Spike Protein of SARS-CoV-2 Omicron BA.5 Inhibits Spike/Integrins Interaction and Viral Infection of Human Lung Microvascular Endothelial Cells

“…Proteome analysis confirmed a dramatic remodeling of SARS-CoV-2-infected HL-mECs, whereas inhibition of Spike RGD/integrins interaction resulted in blocking SARS-CoV-2 infection and in a complete recovery of viral-induced HL-mEC dysfunction [ 20 , 21 ]. More recently, other studies confirmed the capability of SARS-CoV-2 to infect different ECs [ 59 , 60 , 61 ] and defined the role of vimentin [ 62 ] and heparan sulfates [ 63 ] in maintaining and increasing the binding affinity of the viral Spike protein to the EC surface, facilitating SARS-CoV-2 entry.…”