title: Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL.
authors.forename: Neil
authors.initials: N
authors.lastname: Duggal
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL; Department of Bioengineering, University of Illinois at Chicago, IL.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Jaishankar
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL.
authors.forename: Tejabhiram
authors.initials: T
authors.lastname: Yadavalli
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL.
authors.forename: Satvik
authors.initials: S
authors.lastname: Hadigal
authors.affiliation: Functional Nanomaterials, Institute for Materials Science, Kiel University, Kiel, Germany.
authors.forename: Yogendra Kumar
authors.initials: YK
authors.lastname: Mishra
authors.affiliation: Functional Nanomaterials, Institute for Materials Science, Kiel University, Kiel, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Adelung
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, IL; Department of Bioengineering, University of Illinois at Chicago, IL; Department of Microbiology and Immunology, University of Illinois at Chicago, IL.
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects / Q000473:pathology* / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000821:virology; D019573:Epithelium, Corneal / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D034421:Sus scrofa; D013937:Thymidine Kinase / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects; D015034:Zinc Oxide / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D013937:Thymidine Kinase; D015034:Zinc Oxide