title: Expression of herpes virus entry mediator (HVEM) in the cornea and trigeminal ganglia of normal and HSV-1 infected mice.
abstract: OBJECTIVE
  Herpes virus entry mediator (HVEM) plays a critical role in the regulation of inflammation through interaction with its natural ligands LIGHT and lymphotoxin alpha and also serves as one of the entry receptors of herpes simplex virus (HSV). The purpose of this study was to better understand the expression of HVEM in the cornea and trigeminal ganglia (TG), which are important targets of HSV infection.
  
  
  METHODS
  Immunohistochemistry was used to define HVEM expression in the cornea and TG of normal and HSV-1 infected mice euthanized 2 to 5 days or 7 months following corneal inoculation of virus.
  
  
  RESULTS
  We found that HVEM is widely expressed in the normal corneal epithelium and endothelium, is weakly and focally expressed in the corneal stroma, and is expressed in a portion of neurons and non-neuronal cells in the TG. Acute HSV-1 keratitis and ganglionitis were associated with increased HVEM expression in the corneal epithelium and stroma and in neurons and non-neuronal cells of TG, and many inflammatory cells in these tissues also expressed HVEM. TG derived from mice 7 months after virus inoculation demonstrated latent HSV-1 infection that was associated with increased HVEM expression in neurons and non-neuronal cells relative to uninfected control tissues. Latent TG also contained focal infiltrates of mononuclear inflammatory cells, many of which expressed HVEM. Corneas derived from latently infected mice demonstrated chronic keratitis, with no evidence of virus replication or increased HVEM expression in the corneal epithelium, and inflammatory cells present showed only weak HVEM expression.
  
  
  CONCLUSIONS
  HVEM is expressed in the cornea and TG and therefore may serve as an HSV entry receptor in these tissues. Furthermore, these findings raise the possibility that changes in HVEM expression following ocular HSV-1 infection can modulate HSV spread and infection-induced inflammation in the cornea and TG.
authors.affiliation: Department of Pathology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60612, USA.
authors.forename: S Krisztian
authors.initials: SK
authors.lastname: Kovacs
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Emese
authors.initials: E
authors.lastname: Prandovszky
authors.forename: Sandor
authors.initials: S
authors.lastname: Dosa
authors.forename: Sarolta
authors.initials: S
authors.lastname: Bacsa
authors.forename: Klara
authors.initials: K
authors.lastname: Valyi-Nagy
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
mesh_terms: D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D003315:Cornea / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006224:Cricetinae; D005260:Female; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000821:virology; D016849:Keratitis, Herpetic / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000096:biosynthesis* / Q000235:genetics; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D053586:Virus Internalization; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D053240:Receptors, Tumor Necrosis Factor, Member 14