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Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas

PURPOSE: Infection of the human cornea by herpes simplex virus type-1 (HSV-1) can cause significant vision loss. The purpose of this study was to develop an ex vivo model to visualize viral growth and spread in the cornea. The model was also used to analyze cytokine production and study the antivira...

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Autores principales: Duggal, Neil, Jaishankar, Dinesh, Yadavalli, Tejabhiram, Hadigal, Satvik, Mishra, Yogendra Kumar, Adelung, Rainer, Shukla, Deepak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334001/
https://www.ncbi.nlm.nih.gov/pubmed/28275313
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author Duggal, Neil
Jaishankar, Dinesh
Yadavalli, Tejabhiram
Hadigal, Satvik
Mishra, Yogendra Kumar
Adelung, Rainer
Shukla, Deepak
author_facet Duggal, Neil
Jaishankar, Dinesh
Yadavalli, Tejabhiram
Hadigal, Satvik
Mishra, Yogendra Kumar
Adelung, Rainer
Shukla, Deepak
author_sort Duggal, Neil
collection PubMed
description PURPOSE: Infection of the human cornea by herpes simplex virus type-1 (HSV-1) can cause significant vision loss. The purpose of this study was to develop an ex vivo model to visualize viral growth and spread in the cornea. The model was also used to analyze cytokine production and study the antiviral effects of zinc oxide tetrapods. METHODS: A β-galactosidase-expressing recombinant virus, HSV-1(KOS)tk12, was used to demonstrate the ability of the virus to enter and develop blue plaques on human corneal epithelial (HCE) cells and corneal tissues. Freshly obtained porcine corneas were cultured and then scratched before infection with HSV-1(KOS)tk12. The blue plaques on the corneas were imaged using a stereomicroscope. Western blot analysis for HSV-1 proteins was performed to verify HSV-1 infection of the cornea. Using the ex vivo model, zinc oxide tetrapods were tested for their anti-HSV-1 potential, and a cytokine profile was developed to assess the effects of the treatment. RESULTS: Cultured corneas and the use of β-galactosidase-expressing HSV-1(KOS)tk12 virus can provide an attractive ex vivo model to visualize and study HSV-1 entry and spread of the infection in tissues. We found that unlike cultured HCE cells, which demonstrated nearly 100% infectivity, HSV-1 infection of the cultured cornea was more restrictive and took longer to develop. We also found that the zinc oxide tetrapod–shaped nano- and microstructures inhibited HSV infection of the cultured cells, as well as the cultured corneas. The cytokine profile of the infected samples was consistent with previous studies of HSV-1 corneal infection. CONCLUSIONS: The ability to visualize HSV-1 growth and spread in corneal tissues can provide new details about HSV-1 infection of the cornea and the efficacy of new cornea-specific antiviral drug candidates. The ex vivo model also demonstrates antiviral effects of zinc oxide tetrapods and adequately portrays the drug delivery issues that cornea-specific treatments face.
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spelling pubmed-53340012017-03-08 Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas Duggal, Neil Jaishankar, Dinesh Yadavalli, Tejabhiram Hadigal, Satvik Mishra, Yogendra Kumar Adelung, Rainer Shukla, Deepak Mol Vis Research Article PURPOSE: Infection of the human cornea by herpes simplex virus type-1 (HSV-1) can cause significant vision loss. The purpose of this study was to develop an ex vivo model to visualize viral growth and spread in the cornea. The model was also used to analyze cytokine production and study the antiviral effects of zinc oxide tetrapods. METHODS: A β-galactosidase-expressing recombinant virus, HSV-1(KOS)tk12, was used to demonstrate the ability of the virus to enter and develop blue plaques on human corneal epithelial (HCE) cells and corneal tissues. Freshly obtained porcine corneas were cultured and then scratched before infection with HSV-1(KOS)tk12. The blue plaques on the corneas were imaged using a stereomicroscope. Western blot analysis for HSV-1 proteins was performed to verify HSV-1 infection of the cornea. Using the ex vivo model, zinc oxide tetrapods were tested for their anti-HSV-1 potential, and a cytokine profile was developed to assess the effects of the treatment. RESULTS: Cultured corneas and the use of β-galactosidase-expressing HSV-1(KOS)tk12 virus can provide an attractive ex vivo model to visualize and study HSV-1 entry and spread of the infection in tissues. We found that unlike cultured HCE cells, which demonstrated nearly 100% infectivity, HSV-1 infection of the cultured cornea was more restrictive and took longer to develop. We also found that the zinc oxide tetrapod–shaped nano- and microstructures inhibited HSV infection of the cultured cells, as well as the cultured corneas. The cytokine profile of the infected samples was consistent with previous studies of HSV-1 corneal infection. CONCLUSIONS: The ability to visualize HSV-1 growth and spread in corneal tissues can provide new details about HSV-1 infection of the cornea and the efficacy of new cornea-specific antiviral drug candidates. The ex vivo model also demonstrates antiviral effects of zinc oxide tetrapods and adequately portrays the drug delivery issues that cornea-specific treatments face. Molecular Vision 2017-02-26 /pmc/articles/PMC5334001/ /pubmed/28275313 Text en Copyright © 2017 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Duggal, Neil
Jaishankar, Dinesh
Yadavalli, Tejabhiram
Hadigal, Satvik
Mishra, Yogendra Kumar
Adelung, Rainer
Shukla, Deepak
Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
title Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
title_full Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
title_fullStr Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
title_full_unstemmed Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
title_short Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
title_sort zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334001/
https://www.ncbi.nlm.nih.gov/pubmed/28275313
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