Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface
| Autor: | Lyle Armstrong, Joseph Collin, Paul Rooney, Rachel Queen, Majlinda Lako, Agatha Joseph, Steven Lisgo, Ivo Djidrovski, Maria Georgiou, Rafiqul Hussain, Jonathan Coxhead, Birthe Dorgau, Darin Zerti, Francisco C. Figueiredo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Conjunctiva Biology tmprss2 Article Cornea 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Viral entry medicine Tropism Corneal epithelium ace2 Embryonic stem cell Epithelium eye diseases Cell biology Ophthalmology sars-cov-2 030104 developmental biology medicine.anatomical_structure 030221 ophthalmology & optometry sense organs |
| Zdroj: | The Ocular Surface |
| ISSN: | 1937-5913 1542-0124 |
| Popis: | Purpose The high infection rate of SARS-CoV-2 necessitates the need for multiple studies identifying the molecular mechanisms that facilitate the viral entry and propagation. Currently the potential extra-respiratory transmission routes of SARS-CoV-2 remain unclear. Methods Using single-cell RNA Seq and ATAC-Seq datasets and immunohistochemical analysis, we investigated SARS-CoV-2 tropism in the embryonic, fetal and adult human ocular surface. Results The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2+TMPRSS2+ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface. Conclusions Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection. |
| Databáze: | OpenAIRE |
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