Stem Cell Reports . Conjunctival epithelial cells resist productive SARS-CoV-2 infection

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Stem Cell Reports


. 2022 Jun 3;S2213-6711(22)00270-3.
doi: 10.1016/j.stemcr.2022.05.017. Online ahead of print.
Conjunctival epithelial cells resist productive SARS-CoV-2 infection


Robert M Jackson ¹ , Catherine F Hatton ² , Jarmila Stremenova Spegarova ² , Maria Georgiou ¹ , Joseph Collin ¹ , Emily Stephenson ¹ , Bernard Verdon ¹ , Iram J Haq ² , Rafiqul Hussain ¹ , Jonathan M Coxhead ¹ , Hardeep-Singh Mudhar ³ , Bart Wagner ⁴ , Megan Hasoon ¹ , Tracey Davey ⁴ , Paul Rooney ⁵ , C M Anjam Khan ¹ , Chris Ward ¹ , Malcolm Brodlie ² , Muzlifah Haniffa ⁶ , Sophie Hambleton ² , Lyle Armstrong ¹ , Francisco Figueiredo ⁷ , Rachel Queen ⁸ , Christopher J A Duncan ⁹ , Majlinda Lako ¹⁰



Affiliations

• PMID: 35750043
• PMCID: PMC9222349
• DOI: 10.1016/j.stemcr.2022.05.017

Free PMC article

Abstract

Conjunctival epithelial cells, which express viral-entry receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (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 basal, suprabasal, and superficial epithelial cells, and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA sequencing (RNA-seq), with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to severe acute respiratory syndrome coronavirus 2 (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-κB 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 transplantation.

Keywords: ACE2; IFN; NFKB; SARS-CoV-2; TMPRSS2; conjunctiva; conjunctival epithelium; ocular surface; productive infection.