Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium.
Angiotensin-Converting Enzyme 2
Betacoronavirus
/ physiology
COVID-19
Child
Coronavirus Infections
/ metabolism
Epithelial Cells
/ metabolism
Gene Expression Profiling
Gene Expression Regulation
Genetic Variation
Host-Pathogen Interactions
Humans
Inflammation
Interferons
/ metabolism
Interleukin-13
/ metabolism
Middle Aged
Nasal Mucosa
/ metabolism
Pandemics
Peptidyl-Dipeptidase A
/ genetics
Pneumonia, Viral
/ metabolism
SARS-CoV-2
Serine Endopeptidases
/ genetics
Virus Internalization
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 10 2020
12 10 2020
Historique:
received:
09
04
2020
accepted:
08
09
2020
entrez:
13
10
2020
pubmed:
14
10
2020
medline:
27
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33046696
doi: 10.1038/s41467-020-18781-2
pii: 10.1038/s41467-020-18781-2
pmc: PMC7550582
doi:
Substances chimiques
IL13 protein, human
0
Interleukin-13
0
Interferons
9008-11-1
Peptidyl-Dipeptidase A
EC 3.4.15.1
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5139Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES015794
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL128439
Pays : International
Organisme : NIEHS NIH HHS
ID : HHSN268201600032C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141992
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141845
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL107202
Pays : International
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009080
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL138626
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL117626
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL135156
Pays : International
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL132821
Pays : International
Organisme : NHLBI NIH HHS
ID : P01 HL107202
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL140218
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL117004
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL135156
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007546
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD)
ID : MD010443
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL128439
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117004
Pays : United States
Organisme : NIMHD NIH HHS
ID : P60 MD006902
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL132821
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD010443
Pays : United States
Commentaires et corrections
Type : UpdateOf
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