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Updated: May 28, 2026

Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
Differential Gene Expression in Human Upper Respiratory Tract Samples Identifies Antiviral Responses in Omicron
Andrea E Luquette1,2, Anthony Cicalo1,2, Maren C Fitzpatrick1,2
1Genomics and Bioinformatics Department, Biological Defense Research Directorate, Naval Medical Research Command-Frederick, Fort Detrick, MD 21702, USA.
None:
Background/Objectives: SARS-CoV-2 is the causative agent of COVID-19, an infectious viral respiratory disease with human-to-human transmission. Current molecular understanding of how hosts respond to infection by respiratory viral pathogens in general and to SARS-CoV-2 in particular is still a research field under development. The activation levels of various host pathways are dependent on several variables, including the host tissue compartment. Methods: In this work, Illumina RNA sequencing was performed to assess the transcriptional host response to SARS-CoV-2 infection using COVID-19 PCR testing nasopharyngeal (NP) swab remnants from twenty infected and nine non-infected individuals. Results: Differential gene expression (DGE) analysis identified 182 overexpressed genes, with strong enrichment in innate immune and viral response genes. This included a significant induction of IFIH1/MDA5, a pattern recognition receptor (PRR) gene participating in the initial sensing of viral RNAs and subsequent cascade activation of interferon (IFN) and IFN-stimulated genes (ISGs). Interestingly, we observed different levels of concordance with previous similar studies and a significant induction of RIG1 and TLR3, two PRR genes encoding proteins that function to upregulate IFN and ISGs, but which are not normally identified as differentially expressed genes (DEGs). Finally, the overexpression of MX1, a well-characterized biomarker of viral infection; IFIT1, one of the top upregulated genes; and OAS1, OAS2 and OAS3, genes with a molecular function, 2-5-oligoadenylate synthase activity, identified as enriched in the DGE analyses, was confirmed by RT-qPCR. Conclusions: This study provides insights into upper respiratory tract responses to SARS-CoV-2 infections and identifies a set of differentially expressed genes (DEGs) with potential as candidates for further investigations as viral infection biomarkers.
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