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

TitleType 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium.
Publication TypeJournal Article
Year of Publication2020
AuthorsSajuthi, SP, DeFord, P, Jackson, ND, Montgomery, MT, Everman, JL, Rios, CL, Pruesse, E, Nolin, JD, Plender, EG, Wechsler, ME, Mak, ACy, Eng, C, Salazar, S, Medina, V, Wohlford, EM, Huntsman, S, Nickerson, DA, Germer, S, Zody, MC, Abecasis, G, Kang, HMin, Rice, KM, Kumar, R, Oh, S, Rodriguez-Santana, J, Burchard, EG, Seibold, MA
JournalbioRxiv
Date Published2020 Apr 10
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 and , that vary in frequency across world populations. Importantly, we find 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 expression. Finally, we define airway responses to coronavirus infections in children, finding that these infections upregulate 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.

DOI10.1101/2020.04.09.034454
Alternate JournalbioRxiv
PubMed ID32511326
PubMed Central IDPMC7239056
Grant ListR01 ES015794 / ES / NIEHS NIH HHS / United States
HHSN268201600032C / ES / NIEHS NIH HHS / United States
R01 HL141992 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
UM1 HG008901 / HG / NHGRI NIH HHS / United States
R01 HL141845 / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
R01 HL128439 / HL / NHLBI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States
U01 HL138626 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
P01 HL107202 / HL / NHLBI NIH HHS / United States
K01 HL140218 / HL / NHLBI NIH HHS / United States
R01 HL135156 / HL / NHLBI NIH HHS / United States
T32 GM007546 / GM / NIGMS NIH HHS / United States
R01 HL117004 / HL / NHLBI NIH HHS / United States
P60 MD006902 / MD / NIMHD NIH HHS / United States
P01 HL132821 / HL / NHLBI NIH HHS / United States
R01 MD010443 / MD / NIMHD NIH HHS / United States