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Lookup NU author(s): Robert Jackson, Catherine Hatton, Dr Jarmila SpegarovaORCiD, Dr Maria Georgiou, Dr Joseph Collin, Emily Stephenson, Dr Bernard VerdonORCiD, Dr Iram Haq, Raf Hussain, Dr Jonathan Coxhead, Dr Megan Hasoon, Dr Anjam KhanORCiD, Professor Christopher WardORCiD, Dr Malcolm BrodlieORCiD, Professor Muzlifah Haniffa, Professor Sophie HambletonORCiD, Professor Lyle ArmstrongORCiD, Professor Francisco FigueiredoORCiD, Dr Rachel QueenORCiD, Dr Christopher DuncanORCiD, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Although tropism of SARS-CoV-2 for respiratory tract epithelial cells is well established, an open question is whether the conjunctival epithelium is also a target for SARS-CoV-2. Conjunctival epithelial cells, which express viral entry receptors ACE2 and TMPRSS2, constitute the largest exposed epithelium of the ocular surface tissue, and may represent a relevant viral entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of progenitor, basal and superficial epithelial cells and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA Seq, with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to SARS-CoV-2 genome expression, a productive infection did not ensue. The early innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust autocrine and paracrine NF-Kβ activity, without activation of antiviral interferon signalling. Collectively, these data enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications for the design of preventive strategies and conjunctival transplants.
Author(s): Jackson RM, Hatton CF, Spegarova JS, Georgiou M, Collin J, Stephenson E, Verdon B, Haq IJ, Hussain R, Coxhead JM, Mudhar H-S, Wagner B, Hasoon M, Davey T, Rooney P, Khan A, Ward C, Brodlie M, Haniffa M, Hambleton S, Armstrong L, Figueiredo F, Queen R, Duncan CJ, Lako M
Publication type: Article
Publication status: Published
Journal: Stem Cell Reports
Year: 2022
Volume: 17
Issue: 7
Pages: 1699-1713
Print publication date: 12/07/2022
Online publication date: 23/06/2022
Acceptance date: 20/05/2022
Date deposited: 26/06/2023
ISSN (electronic): 2213-6711
Publisher: Cell Press
URL: https://doi.org/10.1016/j.stemcr.2022.05.017
DOI: 10.1016/j.stemcr.2022.05.017
Data Access Statement: The scRNA-seq data datasets produced in this study are deposited in the Gene Expression Omnibus. The accession number is GEO: GSE191232. Analysis scripts and codes are available at https://github.com/RachelQueen1/conjunctival_covid.
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