Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium
| Autor: | Kenneth Rice, Elmar Pruesse, Satria Sajuthi, Hyun Min Kang, Michael E. Wechsler, Peter DeFord, Jamie L. Everman, Gonçalo R. Abecasis, Esteban G. Burchard, Michael C. Zody, Jose R. Rodriguez-Santana, A.C.Y. Mak, Sam S. Oh, James D. Nolin, Max A. Seibold, Vivian Medina, Eric M. Wohlford, Scott Huntsman, Sandra Salazar, Cydney Rios, Elizabeth G. Plender, M.T. Montgomery, Nathan D. Jackson, Deborah A. Nickerson, Soren Germer, Rajesh Kumar, Celeste Eng |
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| Rok vydání: | 2020 |
| Předmět: |
viruses
0302 clinical medicine Interferon Cytotoxic T cell 2.1 Biological and endogenous factors Aetiology Child Receptor Lung Infectivity 0303 health sciences Interleukin-13 Serine Endopeptidases Middle Aged respiratory system 3. Good health Mechanisms of disease Infectious Diseases 030220 oncology & carcinogenesis Host-Pathogen Interactions Pneumonia & Influenza Respiratory Angiotensin-Converting Enzyme 2 medicine.symptom Coronavirus Infections Infection medicine.drug Pneumonia Viral Inflammation Peptidyl-Dipeptidase A Biology Article Vaccine Related Betacoronavirus 03 medical and health sciences Immune system Clinical Research Biodefense medicine Genetics Humans Transcriptomics Pandemics 030304 developmental biology SARS-CoV-2 Gene Expression Profiling Prevention Inflammatory and immune system COVID-19 Genetic Variation Epithelial Cells Pneumonia Virus Internalization Gene regulation Nasal Mucosa Emerging Infectious Diseases Gene Expression Regulation Viral infection Immunology Expression quantitative trait loci Respiratory epithelium Interferons |
| Zdroj: | bioRxiv : the preprint server for biology, vol 1, iss 05-20 bioRxiv article-version (status) pre article-version (number) 1 Nature Communications |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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