Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, an emerging virus that utilizes host proteins ACE2 and TMPRSS2 as entry factors. Understanding the factors affecting the pattern and levels of expression of these genes is important for deeper understanding of SARS-CoV-2 tropism and pathogenesis. Here we explore the role of genetics and co-expression networks in regulating these genes in the airway, through the analysis of nasal airway transcriptome data from 695 children. We identify expression quantitative trait loci for both ACE2 and TMPRSS2 , that vary in frequency across world populations. We find TMPRSS2 is part of a mucus secretory network, highly upregulated by type 2 (T2) inflammation through the action of interleukin-13, and that the interferon response to respiratory viruses highly upregulates ACE2 expression. IL-13 and virus infection mediated effects on ACE2 expression were also observed at the protein level in the airway epithelium. Finally, we define airway responses to common coronavirus infections in children, finding that these infections generate host responses similar to other viral species, including upregulation of IL6 and ACE2 . Our results reveal possible mechanisms influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes. ACE2 and TMPRSS2 have received recent attention as entry factors for SARS-CoV-2. Here the authors analyze nasal airway transcriptome data from 695 children determining ACE2 and TMPRSS2 expression is induced by viral and type2 inflammation, respectively, and both exhibit eQTLs that vary across world populations.
【저자키워드】 viral infection, transcriptomics, Mechanisms of disease, Gene regulation, TMPRSS2, 【초록키워드】 COVID-19, Transcriptome, SARS-CoV-2, Inflammation, Coronavirus infection, Coronavirus disease 2019, ACE2, Pathogenesis, children, eQTL, Infection, IL6, nasal, host response, virus, genetics, clinical outcomes, airway, respiratory virus, response, Factors, understanding, co-expression network, virus infection, ACE2 expression, expression, Quantitative, mechanism, IL-13, Frequency, Analysis, airway epithelium, interleukin-13, Factor, host protein, TMPRSS2 expression, upregulation, loci, protein level, Effect, populations, identify, caused, generate, upregulated, the interferon, affecting, upregulate, 【제목키워드】 Inflammation, interferon, expression, airway epithelium, regulate, SARS-CoV-2 entry, Type,