RT Journal Article
SR Electronic
T1 Delayed induction of type I and III interferons and nasal epithelial cell permissiveness to SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.17.431591
DO 10.1101/2021.02.17.431591
A1 Catherine F Hatton
A1 Rachel A Botting
A1 Maria Emilia Dueñas
A1 Iram J Haq
A1 Bernard Verdon
A1 Benjamin J Thompson
A1 Jarmila Stremenova Spegarova
A1 Florian Gothe
A1 Emily Stephenson
A1 Aaron I Gardner
A1 Sandra Murphy
A1 Jonathan Scott
A1 James P Garnett
A1 Sean Carrie
A1 Rafiqul Hussain
A1 Jonathan Coxhead
A1 Tracey Davey
A1 A John Simpson
A1 Muzlifah Haniffa
A1 Sophie Hambleton
A1 Malcolm Brodlie
A1 Chris Ward
A1 Matthias Trost
A1 Gary Reynolds
A1 Christopher J A Duncan
YR 2021
UL http://biorxiv.org/content/early/2021/02/17/2021.02.17.431591.abstract
AB 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 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 applied single-cell RNA sequencing and proteomics to a primary cell model of human primary nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrated widespread tropism for nasal epithelial cell types. The host response was dominated by type I and III IFNs and interferon-stimulated gene products. Nevertheless, this response was notably delayed in onset compared to viral gene expression, and thus failed to impact substantially on SARS-CoV-2 replication. However, when provided prior to infection, recombinant IFNβ or IFNλ1 induced an efficient antiviral state that potently restricted SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy.Competing Interest StatementThe authors have declared no competing interest.