title: Herpes simplex virus entry receptor nectin-1 is widely expressed in the murine eye.
abstract: OBJECTIVE
  Nectin-1 belongs to the immunoglobulin superfamily, mediates cell-cell adhesion in cadherin-based adherens junctions, and acts as a receptor for herpes simplex virus (HSV). The goals of this study were (1) to determine whether nectin-1 is expressed in ocular tissue that is an important target of HSV infections and (2) to determine whether HSV type 1 (HSV-1) infection affects nectin-1 expression in the eye.
  
  
  METHODS
  Expression of nectin-1 and HSV-1 protein was determined by immunohistochemical analysis of ocular tissues of untreated BALB/c mice and mice that were euthanized either 7 days or 7 months after corneal inoculation of HSV-1 or sterile tissue-culture medium (mock).
  
  
  RESULTS
  In ocular tissues derived from untreated and mock-infected mice, widespread nectin-1 expression was detected among cells of the corneal epithelium and endothelium, conjunctiva, lens epithelium, ciliary body, iris, choroid, and retina. However, fibroblasts in the corneal stroma and the sclera did not express detectable levels of nectin-1. Ocular tissues from mice euthanized 7 days after corneal inoculation of HSV-1 frequently demonstrated corneal ulceration and inflammation and HSV-1 protein expression in the corneal epithelium, stroma, endothelium, conjunctiva, iris, and ciliary body but rarely in the retina. Ocular tissues from mice euthanized 7 months after HSV-1 inoculation demonstrated corneal epithelial and stromal inflammation, but HSV-1 protein expression was not detected. HSV-1 infection did not lead to a loss of nectin-1 expression in any of the tissues examined. In contrast to uninfected corneas, the inflamed and vascularized stroma of infected corneas contained mononuclear inflammatory cells, vascular cells, and fibroblasts that stained positive for nectin-1.
  
  
  CONCLUSIONS
  Findings report that nectin-1 is widely expressed in murine ocular tissues. Only fibroblasts in the corneal stroma and sclera of uninfected tissues were devoid of nectin-1 expression. HSV-1-infected inflamed corneas contained some stromal fibroblasts with detectable nectin-1 expression, which potentially could be targeted by the virus. Widespread nectin-1 expression in the eye suggests that this receptor may play a role in the pathogenesis of ocular HSV infections.
authors.affiliation: Department of Pathology, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.forename: Veeral
authors.initials: V
authors.lastname: Sheth
authors.forename: Christian
authors.initials: C
authors.lastname: Clement
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Perry
authors.initials: P
authors.lastname: Scanlan
authors.forename: Jerry H
authors.initials: JH
authors.lastname: Kavouras
authors.forename: Lu
authors.initials: L
authors.lastname: Leach
authors.forename: Grace
authors.initials: G
authors.lastname: Guzman-Hartman
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005123:Eye / Q000378:metabolism*; D005260:Female; D018259:Herpesvirus 1, Human; D007124:Immunoenzyme Techniques; D016849:Keratitis, Herpetic / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D000075983:Nectins; D011991:Receptors, Virus / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D011991:Receptors, Virus; D014764:Viral Proteins