Retinal pigment epithelial cells are a potential reservoir for ebola virus in the Human Eye

Justine R. Smith, Shawn Todd, Liam M. Ashander, Theodosia Charitou, Yuefang Ma, Steven Yeh, Ian Crozier, Michael Z. Michael, Binoy Appukuttan, Keryn A. Williams, David Lynn, Glenn A. Marsh

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: Success of Ebola virus (EBOV) as a human pathogen relates at the molecular level primarily to blockade the host cell type I interferon (IFN) antiviral response. Most individuals who survive Ebola virus disease (EVD) develop a chronic disease syndrome: approximately one-quarter of survivors suffer from uveitis, which has been associated with presence of EBOV within the eye. Clinical observations of post-Ebola uveitis indicate involvement of retinal pigment epithelial cells. Methods: We inoculated ARPE-19 human retinal pigment epithelial cells with EBOV, and followed course of infection by immunocytochemistry and measurement of titer in culture supernatant. To interrogate transcriptional responses of infected cells, we combined RNA sequencing with in silico pathway, gene ontology, transcription factor binding site, and network analyses. We measured infection-induced changes of selected transcripts by reverse transcription-quantitative polymerase chain reaction. Results: Human retinal pigment epithelial cells were permissive to infection with EBOV, and supported viral replication and release of virus in high titer. Unexpectedly, 28% of 560 upregulated transcripts in EBOV-infected cells were type I IFN responsive, indicating a robust type I IFN response. Following EBOV infection, cells continued to express multiple immunomodulatory molecules linked to ocular immune privilege. Conclusions: Human retinal pigment epithelial cells may serve as an intraocular reservoir for EBOV, and the molecular response of infected cells may contribute to the persistence of live EBOV within the human eye. Translational Relevance: This bedside-to-bench research links ophthalmic findings in survivors of EVD who suffer from uveitis with interactions between retinal pigment epithelial cells and EBOV.

LanguageEnglish
Article number12
JournalTranslational Vision Science and Technology
Volume6
Issue number4
DOIs
Publication statusPublished - 1 Jul 2017

Keywords

  • Ebola virus
  • Eye
  • Human
  • Infection
  • Pigment epithelial cell

ASJC Scopus subject areas

  • Biomedical Engineering
  • Ophthalmology

Cite this

Smith, J. R., Todd, S., Ashander, L. M., Charitou, T., Ma, Y., Yeh, S., ... Marsh, G. A. (2017). Retinal pigment epithelial cells are a potential reservoir for ebola virus in the Human Eye. Translational Vision Science and Technology, 6(4), [12]. https://doi.org/10.1167/tvst.6.4.12
Smith, Justine R. ; Todd, Shawn ; Ashander, Liam M. ; Charitou, Theodosia ; Ma, Yuefang ; Yeh, Steven ; Crozier, Ian ; Michael, Michael Z. ; Appukuttan, Binoy ; Williams, Keryn A. ; Lynn, David ; Marsh, Glenn A. / Retinal pigment epithelial cells are a potential reservoir for ebola virus in the Human Eye. In: Translational Vision Science and Technology. 2017 ; Vol. 6, No. 4.
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abstract = "Purpose: Success of Ebola virus (EBOV) as a human pathogen relates at the molecular level primarily to blockade the host cell type I interferon (IFN) antiviral response. Most individuals who survive Ebola virus disease (EVD) develop a chronic disease syndrome: approximately one-quarter of survivors suffer from uveitis, which has been associated with presence of EBOV within the eye. Clinical observations of post-Ebola uveitis indicate involvement of retinal pigment epithelial cells. Methods: We inoculated ARPE-19 human retinal pigment epithelial cells with EBOV, and followed course of infection by immunocytochemistry and measurement of titer in culture supernatant. To interrogate transcriptional responses of infected cells, we combined RNA sequencing with in silico pathway, gene ontology, transcription factor binding site, and network analyses. We measured infection-induced changes of selected transcripts by reverse transcription-quantitative polymerase chain reaction. Results: Human retinal pigment epithelial cells were permissive to infection with EBOV, and supported viral replication and release of virus in high titer. Unexpectedly, 28{\%} of 560 upregulated transcripts in EBOV-infected cells were type I IFN responsive, indicating a robust type I IFN response. Following EBOV infection, cells continued to express multiple immunomodulatory molecules linked to ocular immune privilege. Conclusions: Human retinal pigment epithelial cells may serve as an intraocular reservoir for EBOV, and the molecular response of infected cells may contribute to the persistence of live EBOV within the human eye. Translational Relevance: This bedside-to-bench research links ophthalmic findings in survivors of EVD who suffer from uveitis with interactions between retinal pigment epithelial cells and EBOV.",
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Smith, JR, Todd, S, Ashander, LM, Charitou, T, Ma, Y, Yeh, S, Crozier, I, Michael, MZ, Appukuttan, B, Williams, KA, Lynn, D & Marsh, GA 2017, 'Retinal pigment epithelial cells are a potential reservoir for ebola virus in the Human Eye', Translational Vision Science and Technology, vol. 6, no. 4, 12. https://doi.org/10.1167/tvst.6.4.12

Retinal pigment epithelial cells are a potential reservoir for ebola virus in the Human Eye. / Smith, Justine R.; Todd, Shawn; Ashander, Liam M.; Charitou, Theodosia; Ma, Yuefang; Yeh, Steven; Crozier, Ian; Michael, Michael Z.; Appukuttan, Binoy; Williams, Keryn A.; Lynn, David; Marsh, Glenn A.

In: Translational Vision Science and Technology, Vol. 6, No. 4, 12, 01.07.2017.

Research output: Contribution to journalArticle

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AU - Todd, Shawn

AU - Ashander, Liam M.

AU - Charitou, Theodosia

AU - Ma, Yuefang

AU - Yeh, Steven

AU - Crozier, Ian

AU - Michael, Michael Z.

AU - Appukuttan, Binoy

AU - Williams, Keryn A.

AU - Lynn, David

AU - Marsh, Glenn A.

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N2 - Purpose: Success of Ebola virus (EBOV) as a human pathogen relates at the molecular level primarily to blockade the host cell type I interferon (IFN) antiviral response. Most individuals who survive Ebola virus disease (EVD) develop a chronic disease syndrome: approximately one-quarter of survivors suffer from uveitis, which has been associated with presence of EBOV within the eye. Clinical observations of post-Ebola uveitis indicate involvement of retinal pigment epithelial cells. Methods: We inoculated ARPE-19 human retinal pigment epithelial cells with EBOV, and followed course of infection by immunocytochemistry and measurement of titer in culture supernatant. To interrogate transcriptional responses of infected cells, we combined RNA sequencing with in silico pathway, gene ontology, transcription factor binding site, and network analyses. We measured infection-induced changes of selected transcripts by reverse transcription-quantitative polymerase chain reaction. Results: Human retinal pigment epithelial cells were permissive to infection with EBOV, and supported viral replication and release of virus in high titer. Unexpectedly, 28% of 560 upregulated transcripts in EBOV-infected cells were type I IFN responsive, indicating a robust type I IFN response. Following EBOV infection, cells continued to express multiple immunomodulatory molecules linked to ocular immune privilege. Conclusions: Human retinal pigment epithelial cells may serve as an intraocular reservoir for EBOV, and the molecular response of infected cells may contribute to the persistence of live EBOV within the human eye. Translational Relevance: This bedside-to-bench research links ophthalmic findings in survivors of EVD who suffer from uveitis with interactions between retinal pigment epithelial cells and EBOV.

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