Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2

Catherine F. Hatton, Rachel A. Botting, Maria Emilia Dueñas, Iram J. Haq, Bernard Verdon, Benjamin J. Thompson, Jarmila Stremenova Spegarova, Florian Gothe, Emily Stephenson, Aaron I. Gardner, Sandra Murphy, Jonathan Scott, James P. Garnett, Sean Carrie, Jason Powell, C. M. Anjam Khan, Lei Huang, Rafiqul Hussain, Jonathan Coxhead, Tracey Davey, A. John Simpson, Muzlifah Haniffa, Sophie Hambleton, Malcolm Brodlie, Chris Ward, Matthias Trost, Gary Reynolds and Christopher J. A. Duncan ()
Additional contact information
Catherine F. Hatton: Newcastle University
Rachel A. Botting: Newcastle University
Maria Emilia Dueñas: Newcastle University
Iram J. Haq: Newcastle University
Bernard Verdon: Newcastle University
Benjamin J. Thompson: Newcastle University
Jarmila Stremenova Spegarova: Newcastle University
Florian Gothe: Newcastle University
Emily Stephenson: Newcastle University
Aaron I. Gardner: Newcastle University
Sandra Murphy: Newcastle University
Jonathan Scott: Newcastle University
James P. Garnett: Newcastle University
Sean Carrie: Newcastle University
Jason Powell: Newcastle University
C. M. Anjam Khan: Newcastle University
Lei Huang: Newcastle University
Rafiqul Hussain: Newcastle University
Jonathan Coxhead: Newcastle University
Tracey Davey: Newcastle University
A. John Simpson: Newcastle University
Muzlifah Haniffa: Newcastle University
Sophie Hambleton: Newcastle University
Malcolm Brodlie: Newcastle University
Chris Ward: Newcastle University
Matthias Trost: Newcastle University
Gary Reynolds: Newcastle University
Christopher J. A. Duncan: Newcastle University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27318-0

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DOI: 10.1038/s41467-021-27318-0

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