HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

Miner, Jonathan J.; Platt, Derek J.; Ghaznavi, Cyrus; Chandra, Pallavi; Santeford, Andrea; Menos, Amber M.; Dong, Zhenyu; Wang, Erin R.; Qian, Wei; Karozichian, Elysse S.; Philips, Jennifer A.; Apte, Rajendra S.

doi:10.1016/j.celrep.2020.108339

Cited by 45 publications

(65 citation statements)

References 32 publications

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“…In terms of replication on the ocular surface, adenoviruses and the herpes simplex virus 1 (HSV-1) are well known to replicate efficiently on the ocular surface [ 136 , 137 ]. In virus-infected cells, double-stranded RNA, which is produced in the cytoplasm by viral replication, acts as an inducer to induce the expression of type I and type III IFNs and IFN-stimulated genes (ISGs), resulting in intracellular antiviral activity [ 136 , 138 , 139 , 140 ].…”

Section: Discussionmentioning

confidence: 99%

“…In virus-infected cells, double-stranded RNA, which is produced in the cytoplasm by viral replication, acts as an inducer to induce the expression of type I and type III IFNs and IFN-stimulated genes (ISGs), resulting in intracellular antiviral activity [ 136 , 138 , 139 , 140 ]. Blockage of the IFN gamma (known as type III interferon) receptor (IFNgR1) increased susceptibility of the HSV-1 virus; however, interestingly SARS-CoV-2 did not replicate on the cornea [ 137 ], suggesting that SARS-CoV-2 infection is mediated by pathways other than IFNgR1 signaling, leading to delay the innate immune response.…”

Section: Discussionmentioning

confidence: 99%

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The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies

Kitazawa

Deinhardt‐Emmer

Inomata

et al. 2021

Cells

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions. Our review focuses on the viral entry mechanisms to give a better understanding of the interaction between SARS-CoV-2 and the eye. We highlighted findings that give evidence for multiple potential receptors of SARS-CoV-2 on the ocular surface. Additionally, we focused on data concerning the detection of viral RNA and its spike protein in the various ocular tissues from patients. However, the expression level seemed to be relatively low compared to the respiratory tissues as a result of a unique environment surrounding the ocular surface and the innate immune response of SARS-CoV-2. Nevertheless, our review suggests the ocular surface as a potential route for SARS-CoV-2 transmission, and as a result of this study we strongly recommend the protection of the eyes for ophthalmologists and patients at risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies

Kitazawa

Deinhardt‐Emmer

Inomata

et al. 2021

Cells

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“…The type III IFN system protects barriers (61), including the female reproductive tract in Zika (62). Recent work has identified Type III IFN signaling on the ocular surface, with corneal epithelium also expressing both subunits of IFNlR1 (63). Expression of type III IFNs and IFNR1l is consistent with FIGURE 4 | Network of interactions between differentially expressed genes and the first-order interactors of these genes or their encoded products in ZIKV-infected human iris pigment epithelial cell isolates from 20 individual donors.…”

Section: Discussionmentioning

confidence: 99%

Zika Virus Infection of Human Iris Pigment Epithelial Cells

et al. 2021

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During recent Zika epidemics, adults infected with Zika virus (ZIKV) have developed organ-specific inflammatory complications. The most serious Zika-associated inflammatory eye disease is uveitis, which is commonly anterior in type, affecting both eyes and responding to corticosteroid eye drops. Mechanisms of Zika-associated anterior uveitis are unknown, but ZIKV has been identified in the aqueous humor of affected individuals. The iris pigment epithelium is a target cell population in viral anterior uveitis, and it acts to maintain immune privilege within the anterior eye. Interactions between ZIKV and human iris pigment epithelial cells were investigated with infectivity assays and RNA-sequencing. Primary cell isolates were prepared from eyes of 20 cadaveric donors, and infected for 24 hours with PRVABC59 strain ZIKV or incubated uninfected as control. Cytoimmunofluorescence, RT-qPCR on total cellular RNA, and focus-forming assays of culture supernatant showed cell isolates were permissive to infection, and supported replication and release of infectious ZIKV. To explore molecular responses of cell isolates to ZIKV infection at the whole transcriptome level, RNA was sequenced on the Illumina NextSeq 500 platform, and results were aligned to the human GRCh38 genome. Multidimensional scaling showed clear separation between transcriptomes of infected and uninfected cell isolates. Differential expression analysis indicated a vigorous molecular response of the cell to ZIKV: 7,935 genes were differentially expressed between ZIKV-infected and uninfected cells (FDR < 0.05), and 99% of 613 genes that changed at least two-fold were up-regulated. Reactome and KEGG pathway and Gene Ontology enrichment analyses indicated strong activation of viral recognition and defense, in addition to biosynthesis processes. A CHAT network included 6275 molecular nodes and 24 contextual hubs in the cell response to ZIKV infection. Receptor-interacting serine/threonine kinase 1 (RIPK1) was the most significantly connected contextual hub. Correlation of gene expression with read counts assigned to the ZIKV genome identified a negative correlation between interferon signaling and viral load across isolates. This work represents the first investigation of mechanisms of Zika-associated anterior uveitis using an in vitro human cell model. The results suggest the iris pigment epithelium mounts a molecular response that limits intraocular pathology in most individuals.

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“…They showed that conjunctival ACE-2 receptors have very limited role in transmission of the disease [23]. The study done by JJ Miner, DJ Platt, CM Ghaznavi et al in November 2020 showed that SARSCoV-2 virus do not replicate in human corneal explants [24]. They showed that infection of corneal tissue was extremely rare.…”

Section: Discussionmentioning

confidence: 99%

Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India

Saxena¹

2021

Preprint

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Introduction- Severe Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim of the study is to compare the risk of COVID-19 in long term spectacles wearers with the risk in persons not using spectacles. Objectives- To know the association between infection with SARSCoV-2 and wearing of spectacles. Materials and methods- In this study, 304 patients of Corona virus disease 2019 (COVID-19) were selected. Their spectacles wearing behaviour was assessed through a questionnaire. Spectacles wearing behaviour of general population was obtained from older studies (for comparison). Risk of COVID-19 was calculated in long term spectacles wearers as well as in persons not using spectacles. Chi- Square test was used for statistical analysis. Results- In this study, total 58 patients showed the behavior of using spectacles continuously during day time and always on outdoor activities. The risk of COVID-19 was found 0.48 in spectacles wearing population as compared to 1.35 in population not using spectacles. The calculated risk ratio was 0.36. The protective effectiveness of the spectacles was found statistically significant (p- value .00113). Conclusion- The present study showed that the risk of Covid-19 was about 2- 3 times less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx.

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HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

Cited by 45 publications

References 32 publications

The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies

The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies

Zika Virus Infection of Human Iris Pigment Epithelial Cells

Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India

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