Singularity and Commonality in Response to SARS-CoV-2 in Lung and Colon Cell Models

Area of Science:

• Molecular biology
• Virology
• Genomics

Background:

• COVID-19 exhibits systemic effects beyond the lungs, impacting various organs due to widespread SARS-CoV-2 entry factors.
• Understanding cellular responses to SARS-CoV-2 and SARS-CoV is crucial for research into COVID-19 pathobiology.

Purpose of the Study:

• To compare commonalities and differences in cellular responses to SARS-CoV-2 and SARS-CoV.
• To investigate cell type-specific responses in lung (Calu-3) and gastrointestinal (Caco-2) epithelial cells.
• To identify key molecular pathways and host factors involved in COVID-19 extrapulmonary manifestations.

Main Methods:

• Utilized a multi-modular UNCOVIDING approach for compendium-wide analysis of transcriptomic datasets.
• Performed comparative analysis of differentially expressed genes, canonical pathways, and upstream regulators.
• Analyzed over 19,000 mRNASeq datasets to dissect condition-specific gene signatures.

Main Results:

• Both SARS-CoV-2 and SARS-CoV elicited similar cellular responses in lung and colon cell lines.
• Distinct cell type-specific regulators were identified for Calu-3 and Caco-2 cells.
• Interferon system impacts lung cells, while liver and lipid metabolism are linked to gastrointestinal responses; APOBEC3G identified as a potential antiviral factor.

Conclusions:

• SARS-CoV-2 and SARS-CoV share common cellular response mechanisms but exhibit cell-specific regulatory differences.
• Findings highlight the role of interferon in pulmonary COVID-19 and lipid metabolism in gastrointestinal manifestations.
• APOBEC3G emerges as a significant intrinsic host factor against SARS-CoV-2 infection.