Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2.
Antiviral Agents
/ immunology
COVID-19
/ immunology
Cells, Cultured
Epithelial Cells
/ cytology
Humans
Immunity, Innate
Interferon Type I
/ immunology
Interferons
/ immunology
Kinetics
Nasal Mucosa
/ cytology
SARS-CoV-2
/ drug effects
Signal Transduction
/ drug effects
Viral Tropism
Virus Replication
/ drug effects
Interferon Lambda
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 12 2021
07 12 2021
Historique:
received:
16
02
2021
accepted:
12
11
2021
entrez:
8
12
2021
pubmed:
9
12
2021
medline:
17
12
2021
Statut:
epublish
Résumé
The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we apply single-cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrates widespread tropism for nasal epithelial cell types. The host response is dominated by type I and III IFNs and interferon-stimulated gene products. This response is notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response begins to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFNβ or IFNλ1 induces an efficient antiviral state that potently restricts SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data imply that the IFN-I/III response to SARS-CoV-2 initiates in the nasal airway and suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy.
Identifiants
pubmed: 34876592
doi: 10.1038/s41467-021-27318-0
pii: 10.1038/s41467-021-27318-0
pmc: PMC8651658
doi:
Substances chimiques
Antiviral Agents
0
Interferon Type I
0
Interferons
9008-11-1
Interferon Lambda
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7092Subventions
Organisme : Medical Research Council
ID : MR/V028448/1
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 211153/Z/18/Z
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/NO13840/1
Organisme : Medical Research Council
ID : MR/N02995X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211153/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 207556/Z/17/Z
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : WT107931/Z/15/Z
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/M008797/1
Organisme : Medical Research Council
ID : MC_PC_20060
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 214539/Z/18/Z
Organisme : Wellcome Trust
ID : 207556/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 215542/Z/19/Z
Informations de copyright
© 2021. The Author(s).
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