Toggle Main Menu Toggle Search

Open Access padlockePrints

Conjunctival epithelial cells resist productive SARS-CoV-2 infection

Lookup NU author(s): Robert Jackson, Catherine Hatton, Dr Jarmila SpegarovaORCiD, Dr Maria Georgiou, Dr Joseph Collin, Emily Stephenson, Dr Bernard Verdon, Dr Iram Haq, Raf Hussain, Dr Jonathan Coxhead, Dr Megan Hasoon, Dr Anjam Khan, Professor Christopher WardORCiD, Dr Malcolm Brodlie, Professor Muzlifah Haniffa, Professor Sophie Hambleton, Professor Lyle Armstrong, Professor Francisco FigueiredoORCiD, Dr Rachel Queen, Dr Christopher DuncanORCiD, Professor Majlinda LakoORCiD

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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.


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
211153/Z/18/ZWellcome Trust
BB/R013942/1Biotechnology and Biological Sciences Research Council (BBSRC)
BB/T004460/1
BB/V01126X/1
MR/NO13840/1

Share