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Transcriptomic analysis reveals novel mechanisms of SARS-CoV-2 infection in human lung cells
Shaomin Yang1,2, Songbin Wu1, Zhijian Yu3
1Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
Background:
Severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) is a single-stranded RNA virus responsible for the global pandemic of the coronavirus disease-2019 (COVID-19). To date, there are still no effective approaches for the prevention and treatment of COVID-19.
Objective:
The present study aims to explore the possible mechanisms of SARS-CoV-2 infection in human lung cells.
Methods:
Data interpretation was conducted by recruiting bioinformatics analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis using downloaded data from the NCBI Gene Expression Omnibus database.
Results:
The present study demonstrated that SARS-CoV-2 infection induces the upregulation of 14 interferon-stimulated genes, indicative of immune, and interferon responses to the virus. Notably, genes for pyrimidine metabolism and steroid hormone biosynthesis are selectively enriched in human lung cells after SARS-CoV-2 infection, suggesting that altered pyrimidine metabolism and steroid biosynthesis are remarkable, and perhaps druggable features after SARS-CoV-2 infection. Besides, there is a strong positive correlation between viral ORF1ab, ORF6, and angiotensin-converting enzyme 2 (ACE2) expression in human lung cells, implying that ACE2 facilitates SARS-CoV-2 infection and replication in host cells probably through the induction of ORF1ab and ORF6.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacts human lung cells by altering pyrimidine metabolism and steroid biosynthesis. Angiotensin-converting enzyme 2 (ACE2) may facilitate viral replication.
Area of Science:
- Virology
- Molecular Biology
- Bioinformatics
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease-2019 (COVID-19).
- Effective prevention and treatment strategies for COVID-19 remain limited.
Purpose of the Study:
- To investigate the molecular mechanisms of SARS-CoV-2 infection in human lung cells.
- To identify potential therapeutic targets for COVID-19.
Main Methods:
- Bioinformatics analysis of gene expression data from the NCBI Gene Expression Omnibus database.
- Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.
Main Results:
- SARS-CoV-2 infection upregulates 14 interferon-stimulated genes, indicating immune and interferon responses.
- Enrichment of genes involved in pyrimidine metabolism and steroid hormone biosynthesis in infected lung cells.
- Positive correlation between viral ORF1ab, ORF6, and angiotensin-converting enzyme 2 (ACE2) expression, suggesting ACE2 facilitates viral entry and replication.
Conclusions:
- Altered pyrimidine metabolism and steroid biosynthesis are key features of SARS-CoV-2 infection in lung cells.
- ACE2 plays a role in facilitating SARS-CoV-2 infection and replication.
- These findings suggest potential druggable targets for COVID-19 treatment.
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