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Conjunctival epithelial cells resist productive SARS-CoV-2 infection

Lookup NU author(s): Robert Jackson, Dr Maria Georgiou, Catherine Hatton, Dr Jarmila Spegarova, Dr Rachel Queen, Dr Christopher DuncanORCiD, Professor Majlinda LakoORCiD

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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, Georgiou M, Hatton CF, Spegarova JS, 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

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


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