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

Autor: Sajuthi SP; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., DeFord P; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Jackson ND; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Montgomery MT; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Everman JL; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Rios CL; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Pruesse E; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Nolin JD; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Plender EG; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA., Wechsler ME; Department of Medicine, National Jewish Health, Denver, CO, 80206 USA., Mak AC; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA., Eng C; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA., Salazar S; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA., Medina V; Centro de Neumología Pediátrica, San Juan, Puerto Rico., Wohlford EM; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA.; Division of Pediatric Allergy and Immunology, Therapeutic Sciences University of California San Francisco, San Francisco, CA., Huntsman S; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA., Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.; Northwest Genomics Center, Seattle, WA, USA.; Brotman Baty Institute, Seattle, WA, USA., Germer S; New York Genome Center, NYC, New York., Zody MC; New York Genome Center, NYC, New York., Abecasis G; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA., Kang HM; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA., Rice KM; Department of Biostatistics, University of Washington, Seattle, WA, USA., Kumar R; Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Pediatrics, Northwestern University, Chicago, III., Oh S; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA., Rodriguez-Santana J; Centro de Neumología Pediátrica, San Juan, Puerto Rico., Burchard EG; Department of Medicine, Therapeutic Sciences University of California San Francisco, San Francisco, CA.; Department of Bioengineering and Therapeutic Sciences University of California San Francisco, San Francisco, CA., Seibold MA; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA.; Department of Pediatrics, National Jewish Health, Denver, CO, 80206 USA.; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado-AMC, Aurora, CO, 80045 USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2020 Apr 10. Date of Electronic Publication: 2020 Apr 10.
DOI: 10.1101/2020.04.09.034454
Abstrakt: 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.
Databáze: MEDLINE