Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

Satria P. Sajuthi, Peter DeFord, Nathan D. Jackson, Michael T. Montgomery, Jamie L. Everman, Cydney L. Rios, Elmar Pruesse, James D. Nolin, Elizabeth G. Plender, Michael E. Wechsler, Angel CY Mak, Celeste Eng, Sandra Salazar, Vivian Medina, Eric M. Wohlford, Scott Huntsman, Deborah A. Nickerson, Soren Germer, Michael C. Zody, Gonçalo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar, Sam Oh, Jose Rodriguez-Santana, Esteban G. Burchard, Max A. Seibold
doi: https://doi.org/10.1101/2020.04.09.034454
Satria P. Sajuthi
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter DeFord
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan D. Jackson
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael T. Montgomery
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jamie L. Everman
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cydney L. Rios
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elmar Pruesse
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James D. Nolin
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth G. Plender
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael E. Wechsler
2Department of Medicine, National Jewish Health, Denver, CO, 80206 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angel CY Mak
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Celeste Eng
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra Salazar
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vivian Medina
4Centro de Neumología Pediátrica, San Juan, Puerto Rico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric M. Wohlford
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
5Division of Pediatric Allergy and Immunology, Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott Huntsman
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deborah A. Nickerson
6Department of Genome Sciences, University of Washington, Seattle, WA, USA
7Northwest Genomics Center, Seattle, WA, USA
8Brotman Baty Institute, Seattle, WA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Soren Germer
9New York Genome Center, NYC, New York
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael C. Zody
9New York Genome Center, NYC, New York
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gonçalo Abecasis
10Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyun Min Kang
10Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenneth M. Rice
11Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rajesh Kumar
12Ann and Robert H. Lurie Children’s Hospital of Chicago, Department of Pediatrics, Northwestern University, Chicago, Ill
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sam Oh
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jose Rodriguez-Santana
4Centro de Neumología Pediátrica, San Juan, Puerto Rico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esteban G. Burchard
3Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA
13Department of Bioengineering and Therapeutic Sciences University of California San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Max A. Seibold
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
14Department of Pediatrics, National Jewish Health, Denver, CO, 80206 USA
15Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado-AMC, Aurora, CO, 80045 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: seiboldm@njhealth.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted April 10, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium
Satria P. Sajuthi, Peter DeFord, Nathan D. Jackson, Michael T. Montgomery, Jamie L. Everman, Cydney L. Rios, Elmar Pruesse, James D. Nolin, Elizabeth G. Plender, Michael E. Wechsler, Angel CY Mak, Celeste Eng, Sandra Salazar, Vivian Medina, Eric M. Wohlford, Scott Huntsman, Deborah A. Nickerson, Soren Germer, Michael C. Zody, Gonçalo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar, Sam Oh, Jose Rodriguez-Santana, Esteban G. Burchard, Max A. Seibold
bioRxiv 2020.04.09.034454; doi: https://doi.org/10.1101/2020.04.09.034454
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium
Satria P. Sajuthi, Peter DeFord, Nathan D. Jackson, Michael T. Montgomery, Jamie L. Everman, Cydney L. Rios, Elmar Pruesse, James D. Nolin, Elizabeth G. Plender, Michael E. Wechsler, Angel CY Mak, Celeste Eng, Sandra Salazar, Vivian Medina, Eric M. Wohlford, Scott Huntsman, Deborah A. Nickerson, Soren Germer, Michael C. Zody, Gonçalo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar, Sam Oh, Jose Rodriguez-Santana, Esteban G. Burchard, Max A. Seibold
bioRxiv 2020.04.09.034454; doi: https://doi.org/10.1101/2020.04.09.034454

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3689)
  • Biochemistry (7789)
  • Bioengineering (5674)
  • Bioinformatics (21282)
  • Biophysics (10576)
  • Cancer Biology (8173)
  • Cell Biology (11937)
  • Clinical Trials (138)
  • Developmental Biology (6762)
  • Ecology (10401)
  • Epidemiology (2065)
  • Evolutionary Biology (13863)
  • Genetics (9708)
  • Genomics (13070)
  • Immunology (8139)
  • Microbiology (19983)
  • Molecular Biology (7842)
  • Neuroscience (43053)
  • Paleontology (319)
  • Pathology (1279)
  • Pharmacology and Toxicology (2258)
  • Physiology (3351)
  • Plant Biology (7232)
  • Scientific Communication and Education (1312)
  • Synthetic Biology (2004)
  • Systems Biology (5537)
  • Zoology (1128)