Novel signaling pathways regulate SARS-CoV and SARS-CoV-2 infectious disease

Medicine (Baltimore). 2021 Feb 19;100(7):e24321. doi: 10.1097/MD.0000000000024321.

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 induces severe infection, and it is responsible for a worldwide disease outbreak starting in late 2019. Currently, there are no effective medications against coronavirus. In the present study, we utilized a holistic bioinformatics approach to study gene signatures of SARS-CoV- and SARS-CoV-2-infected Calu-3 lung adenocarcinoma cells. Through the Gene Ontology platform, we determined that several cytokine genes were up-regulated after SARS-CoV-2 infection, including TNF, IL6, CSF2, IFNL1, IL-17C, CXCL10, and CXCL11. Differentially regulated pathways were detected by the Kyoto Encyclopedia of Genes and Genomes, gene ontology, and Hallmark platform, including chemokines, cytokines, cytokine receptors, cytokine metabolism, inflammation, immune responses, and cellular responses to the virus. A Venn diagram was utilized to illustrate common overlapping genes from SARS-CoV- and SARS-CoV-2-infected datasets. An Ingenuity pathway analysis discovered an enrichment of tumor necrosis factor- (TNF-) and interleukin (IL)-17-related signaling in a gene set enrichment analysis. Downstream networks were predicted by the Database for Annotation, Visualization, and Integrated Discovery platform also revealed that TNF and TNF receptor 2 signaling elicited leukocyte recruitment, activation, and survival of host cells after coronavirus infection. Our discovery provides essential evidence for transcript regulation and downstream signaling of SARS-CoV and SARS-CoV-2 infection.

MeSH terms

  • COVID-19 / genetics*
  • COVID-19 / immunology*
  • Cell Line, Tumor
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Gene Expression Profiling
  • Gene Ontology
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-17 / biosynthesis
  • Receptors, Tumor Necrosis Factor, Type II / biosynthesis
  • SARS-CoV-2
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation

Substances

  • Chemokines
  • Cytokines
  • Inflammation Mediators
  • Interleukin-17
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha