Transcriptomic analysis reveals novel mechanisms of SARS-CoV-2 infection in human lung cells

Abstract

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.