Author:
Sajuthi Satria P.,DeFord Peter,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 CY,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.
Abstract
AbstractCoronavirus 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
72 articles.
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