Dataset Information

SUMO pathway, blood coagulation and oxidative stress in SARS-CoV-2 infection.

ABSTRACT: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS CoV-2) is currently an international pandemic causing coronavirus disease 19 (COVID-19). Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2) for membrane fusion or through endosomal pathway. This Study aims to assess transcriptomic changes and differentially expressed genes (DFGs) in COVID-19.

Methods

Transcriptomic data of the publicly available dataset (GSE147507) was quantile normalized and analysed for DFGs, network analysis and pathway analysis.

Results

DFG sets showed that 8 genes (SAE1, AEBP2, ATP1A1, DKK3, MAFF, NUDC, TRAP1, and VAV1) were significantly dysregulated in all studied groups. Functional analysis revealed that negative regulation of glucocorticoid biosynthesis, protein SUMOylation (SAE1), blood coagulation (VAV1) and cellular response to stress were affected by SARS CoV-2 infection. Cell line transduction with ACE2 vector didn't show significant changes in the dysregulated pathways. Also, no significant change was observed in expression levels of ACE2 or TMPRSS2 in response to SARS CoV-2 infection. Further analysis showed dysregulation of several genes in the SUMOylation pathway and blood coagulation process in human and cell lines transcriptome. Also, several Cathepsins proteases were significantly dysregulated in case of SARS CoV-2 infection. Genes related to cellular response to stress such as TRAP-1 and NOX were dysregulated in cases of SARS CoV-2 infection.

Conclusion

Dysregulation in genes of protein SUMOylation, blood coagulation and response to oxidative stress pathways in SARS CoV-2 infection could be critical for disease progression. Drugs acting on SUMO pathway, VAV1, NOX genes could be studied for potential benefit to COVID-19 patients.

SUBMITTER: Ibrahim IH

PROVIDER: S-EPMC7857074 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Severe viral infections, including SARS-COV-2, could trigger disruption of the balance between pro-oxidant and antioxidant mediators; the magnitude of which could reflect the severity of infection and lung injury. Using publicly available COVID-19 transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 125 oxidative stress genes, including 37 pro-oxidant genes, 32 oxidative-responsive genes, and 56 antioxidant genes. Seven oxidative stress genes were found to be upregulated in whole blood and lung autopsies (MPO, S100A8, S100A9, SRXN1, GCLM, SESN2, and TXN); these genes were higher in severe versus non-severe COVID-19 leucocytes. Oxidative genes were upregulated in inflammatory cells comprising macrophages and CD8+ T cells isolated from bronchioalveolar fluid (BALF), and neutrophils isolated from peripheral blood. MPO, S100A8, and S100A9 were top most upregulated oxidative markers within COVID-19's lung autopsies, whole blood, leucocytes, BALF derived macrophages and circulating neutrophils. The calprotectin's, S100A8 and S100A9 were upregulated in SARS-COV-2 infected human lung epithelium. To validate our in-silico analysis, we conducted qRT-PCR to measure MPO and calprotectin's levels in blood and saliva samples. Relative to uninfected donor controls, MPO, S100A8 and S100A9 were significantly higher in blood and saliva of severe versus asymptomatic COVID-19 patients. Compared to other different viral respiratory infections, coronavirus infection showed a prominent upregulation in oxidative stress genes with MPO and calprotectin at the top of the list. In conclusion, SARS-COV-2 induce the expression of oxidative stress genes via both immune as well as lung structural cells. The observed correlation between oxidative stress genes dysregulation and COVID-19 disease severity deserve more attention. Mechanistical studies are required to confirm the correlation between oxidative stress gene dysregulation, COVID-19 severity, and the net oxidative stress balance.