Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium

BioRxiv : the Preprint Server for Biology
Satria SajuthiMax A Seibold

Abstract

Coronavirus disease 2019 (COVID-19) outcomes vary from asymptomatic infection to death. This disparity may reflect different airway levels of the SARS-CoV-2 receptor, ACE2, and the spike protein activator, TMPRSS2. 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 (eQTL) for both ACE2 and TMPRSS2, that vary in frequency across world populations. Importantly, we find TMPRSS2 is part of a mucus secretory network, highly upregulated by T2 inflammation through the action of interleukin-13, and that interferon response to respiratory viruses highly upregulates ACE2 expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate IL6 while also stimulating a more pronounced cytotoxic immune response relative to other respiratory viruses. Our results reveal mechanisms likely influencing SARS-CoV-2 infectivity and COVID-19 clinical outcomes.

Citations

Apr 30, 2020·Nature Reviews. Immunology·Samarth Hegde
Aug 19, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Omalla A OlwenyiSiddappa N Byrareddy
Sep 4, 2020·Human Vaccines & Immunotherapeutics·Patrick O'Connell, Yasser A Aldhamen
Aug 28, 2020·Frontiers in Genetics·Roberta RussoMario Capasso
Sep 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jonathan Baruch SteinmanLawrence Steinman
Jul 6, 2020·Allergy·Jiu-Yao WangWen-Shuo Kuo
Oct 8, 2020·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Sunita Chhapola Shukla
Oct 18, 2020·The Journal of Allergy and Clinical Immunology·Lydia J FinneyAran Singanayagam
Jan 27, 2021·Lung·Grigorios Chatziparasidis, Ahmad Kantar
Mar 2, 2021·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Kam Sing HoDavid Steiger
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Jan 20, 2022·Clinical Reviews in Allergy & Immunology·Jin-Jin ZhangYa-Dong Gao

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Datasets Mentioned

BETA
GSE3982
GSE22886

Methods Mentioned

BETA
glycosylation
scRNA-seq
RNA-seq
PCA

Software Mentioned

gnomAD
skewer 37
Ensembl
BLAT
limma 55 R
limma
BLAST
HISAT2
Seurat
QIAGEN

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