tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Catherine F Hatton[SUP] 2 [/SUP], Jarmila Stremenova Spegarova[SUP] 2 [/SUP], Maria Georgiou[SUP] 1 [/SUP], Joseph Collin[SUP] 1 [/SUP], Emily Stephenson[SUP] 1 [/SUP], Bernard Verdon[SUP] 1 [/SUP], Iram J Haq[SUP] 2 [/SUP], Rafiqul Hussain[SUP] 1 [/SUP], Jonathan M Coxhead[SUP] 1 [/SUP], Hardeep-Singh Mudhar[SUP] 3 [/SUP], Bart Wagner[SUP] 4 [/SUP], Megan Hasoon[SUP] 1 [/SUP], Tracey Davey[SUP] 4 [/SUP], Paul Rooney[SUP] 5 [/SUP], C M Anjam Khan[SUP] 1 [/SUP], Chris Ward[SUP] 1 [/SUP], Malcolm Brodlie[SUP] 2 [/SUP], Muzlifah Haniffa[SUP] 6 [/SUP], Sophie Hambleton[SUP] 2 [/SUP], Lyle Armstrong[SUP] 1 [/SUP], Francisco Figueiredo[SUP] 7 [/SUP], Rachel Queen[SUP] 8 [/SUP], Christopher J A Duncan[SUP] 9 [/SUP], Majlinda Lako[SUP] 10 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Catherine F Hatton[SUP] 2 [/SUP], Jarmila Stremenova Spegarova[SUP] 2 [/SUP], Maria Georgiou[SUP] 1 [/SUP], Joseph Collin[SUP] 1 [/SUP], Emily Stephenson[SUP] 1 [/SUP], Bernard Verdon[SUP] 1 [/SUP], Iram J Haq[SUP] 2 [/SUP], Rafiqul Hussain[SUP] 1 [/SUP], Jonathan M Coxhead[SUP] 1 [/SUP], Hardeep-Singh Mudhar[SUP] 3 [/SUP], Bart Wagner[SUP] 4 [/SUP], Megan Hasoon[SUP] 1 [/SUP], Tracey Davey[SUP] 4 [/SUP], Paul Rooney[SUP] 5 [/SUP], C M Anjam Khan[SUP] 1 [/SUP], Chris Ward[SUP] 1 [/SUP], Malcolm Brodlie[SUP] 2 [/SUP], Muzlifah Haniffa[SUP] 6 [/SUP], Sophie Hambleton[SUP] 2 [/SUP], Lyle Armstrong[SUP] 1 [/SUP], Francisco Figueiredo[SUP] 7 [/SUP], Rachel Queen[SUP] 8 [/SUP], Christopher J A Duncan[SUP] 9 [/SUP], Majlinda Lako[SUP] 10 [/SUP]
Affiliations
- PMID: 35750043
- PMCID: PMC9222349
- DOI: 10.1016/j.stemcr.2022.05.017
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.