SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.
H1N1
SARS-CoV-2
TSPAN8
airway organoids
cell composition
single cell RNAseq
spectral flow
therapeutics
variants
virus
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
14 03 2023
14 03 2023
Historique:
received:
12
12
2022
revised:
23
01
2023
accepted:
24
01
2023
pubmed:
25
2
2023
medline:
21
3
2023
entrez:
24
2
2023
Statut:
ppublish
Résumé
Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.
Identifiants
pubmed: 36827975
pii: S2213-6711(23)00014-0
doi: 10.1016/j.stemcr.2023.01.011
pmc: PMC9948283
pii:
doi:
Substances chimiques
Tetraspanins
0
TSPAN8 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
636-653Subventions
Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI083139
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI091580
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL145235
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI138546
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI077439
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interests The authors have no competing interests. A patent “INHIBITORS OF SARS-COV-2 INFECTION AND OTHER CORONA VIRUS INFECTIONS” SF-2021-201-2-PCT-0 has been filed.
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