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Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2.
Nat Commun. 2021 12 07; 12(1):7092.NC

Abstract

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.

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Authors+Show Affiliations

Hatton CF
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Botting RA
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Dueñas ME
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Haq IJ
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. Paediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Verdon B
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Thompson BJ
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Spegarova JS
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Gothe F
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.
Stephenson E
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Gardner AI
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Murphy S
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Scott J
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Garnett JP
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Carrie S
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Powell J
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Khan CMA
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Huang L
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Hussain R
Genomics Core Facility, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Coxhead J
Genomics Core Facility, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Davey T
Electron Microscopy Research Services, Newcastle University, Newcastle upon Tyne, UK.
Simpson AJ
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Haniffa M
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK. NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Department of Dermatology, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Hambleton S
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Brodlie M
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. Paediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Ward C
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Trost M
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Reynolds G
Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Duncan CJA
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. christopher.duncan@ncl.ac.uk. Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. christopher.duncan@ncl.ac.uk.

MeSH

Antiviral AgentsCOVID-19Cells, CulturedEpithelial CellsHumansImmunity, InnateInterferon Type IInterferonsKineticsNasal MucosaSARS-CoV-2Signal TransductionViral TropismVirus ReplicationInterferon Lambda

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34876592

Citation

Hatton, Catherine F., et al. "Delayed Induction of Type I and III Interferons Mediates Nasal Epithelial Cell Permissiveness to SARS-CoV-2." Nature Communications, vol. 12, no. 1, 2021, p. 7092.
Hatton CF, Botting RA, Dueñas ME, et al. Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2. Nat Commun. 2021;12(1):7092.
Hatton, C. F., Botting, R. A., Dueñas, M. E., Haq, I. J., Verdon, B., Thompson, B. J., Spegarova, J. S., Gothe, F., Stephenson, E., Gardner, A. I., Murphy, S., Scott, J., Garnett, J. P., Carrie, S., Powell, J., Khan, C. M. A., Huang, L., Hussain, R., Coxhead, J., ... Duncan, C. J. A. (2021). Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2. Nature Communications, 12(1), 7092. https://doi.org/10.1038/s41467-021-27318-0
Hatton CF, et al. Delayed Induction of Type I and III Interferons Mediates Nasal Epithelial Cell Permissiveness to SARS-CoV-2. Nat Commun. 2021 12 7;12(1):7092. PubMed PMID: 34876592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2. AU - Hatton,Catherine F, AU - Botting,Rachel A, AU - Dueñas,Maria Emilia, AU - Haq,Iram J, AU - Verdon,Bernard, AU - Thompson,Benjamin J, AU - Spegarova,Jarmila Stremenova, AU - Gothe,Florian, AU - Stephenson,Emily, AU - Gardner,Aaron I, AU - Murphy,Sandra, AU - Scott,Jonathan, AU - Garnett,James P, AU - Carrie,Sean, AU - Powell,Jason, AU - Khan,C M Anjam, AU - Huang,Lei, AU - Hussain,Rafiqul, AU - Coxhead,Jonathan, AU - Davey,Tracey, AU - Simpson,A John, AU - Haniffa,Muzlifah, AU - Hambleton,Sophie, AU - Brodlie,Malcolm, AU - Ward,Chris, AU - Trost,Matthias, AU - Reynolds,Gary, AU - Duncan,Christopher J A, Y1 - 2021/12/07/ PY - 2021/02/16/received PY - 2021/11/12/accepted PY - 2021/12/8/entrez PY - 2021/12/9/pubmed PY - 2021/12/17/medline SP - 7092 EP - 7092 JF - Nature communications JO - Nat Commun VL - 12 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/34876592/Delayed_induction_of_type_I_and_III_interferons_mediates_nasal_epithelial_cell_permissiveness_to_SARS_CoV_2_ DB - PRIME DP - Unbound Medicine ER -