In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control

Background: Angiotensin I converting enzyme 2 (ACE2) is a receptor for the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and differences in its expression may affect susceptibility to infection. Methods: We performed genome-wide quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from 190 individuals. Results: discovered that polymorphism type III interferon gene (IFNL4), which eliminates IFN-λ4 production, associated with two-fold increase ACE2 RNA expression. Conversely, among genes negatively correlated ACE2 expression, IFN-signalling pathways were highly enriched was downregulated after IFN-α treatment. Negative correlation was also found gastrointestinal tract where inflammation driven IFN-stimulated ACE2 lung murine model of SARS-CoV-1 infection suggesting conserved regulation across species. Conclusions: conclude is likely negatively-regulated interferon-stimulated (ISG) carriage IFNL4 gene alleles modulates ISGs viral play role SARS-CoV-2 pathogenesis implications therapeutic interventions.