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

10.1101/2021.02.17.431591

bioRxiv

19th February 2021

Contributing to research themes:

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.

Author list:

Affiliations

1. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

2. Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.

3. Paediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

4. Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig Maximilians-Universität Munich, Munich, Germany.

5. Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.

6. Genomics Core Facility, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK

 

a equal contribution, b equal contribution, * corresponding author

 

Catherine F Hatton1a, Rachel A Botting2a, Maria Emilia Dueñas2a, Iram J Haq1,3a, Bernard Verdon2a, Benjamin J Thompson1, Jarmila Stremenova Spegarova1, Florian Gothe1,4, Emily Stephenson2, Aaron I Gardner1, Sandra Murphy2, Jonathan Scott1, James P Garnett1, Sean Carrie5, Rafiqul Hussain6, Jonathan Coxhead6, Tracey Davey7, A John Simpson1, Muzlifah Haniffa2,8,9,10, Sophie Hambleton1,11, Malcolm Brodlie1,3b, Chris Ward1b, Matthias Trost2b, Gary Reynolds2b, Christopher J A Duncan1,12 b *