Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

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 pathog...

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Vydáno v:	Nature communications Ročník 11; číslo 1; s. 5139 - 18
Hlavní autoři:	Sajuthi, Satria P., DeFord, Peter, Li, Yingchun, Jackson, Nathan D., Montgomery, Michael T., Everman, Jamie L., Rios, Cydney L., Pruesse, Elmar, Nolin, James D., Plender, Elizabeth G., Wechsler, Michael E., Mak, Angel C. Y., Eng, Celeste, Salazar, Sandra, Medina, Vivian, Wohlford, Eric M., Huntsman, Scott, Nickerson, Deborah A., Germer, Soren, Zody, Michael C., Abecasis, Gonçalo, Kang, Hyun Min, Rice, Kenneth M., Kumar, Rajesh, Oh, Sam, Rodriguez-Santana, Jose, Burchard, Esteban G., Seibold, Max A.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 12.10.2020 Nature Portfolio
Témata:	13/106 38 38/91 631/208/200 631/337/2019 631/80/304 692/699/255/2514 Angiotensin-Converting Enzyme 2 Betacoronavirus - physiology Child Coronavirus Infections - metabolism Coronavirus Infections - pathology Coronavirus Infections - virology COVID-19 Epithelial Cells - metabolism Gene Expression Profiling Gene Expression Regulation Genetic Variation Host-Pathogen Interactions Humanities and Social Sciences Humans Inflammation Interferons - metabolism Interleukin-13 - metabolism Middle Aged multidisciplinary Nasal Mucosa - metabolism Nasal Mucosa - pathology Pandemics Peptidyl-Dipeptidase A - genetics Peptidyl-Dipeptidase A - metabolism Pneumonia, Viral - metabolism Pneumonia, Viral - pathology Pneumonia, Viral - virology SARS-CoV-2 Science Science (multidisciplinary) Serine Endopeptidases - genetics Serine Endopeptidases - metabolism Virus Internalization
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-18781-2