Faculty Collaboration Database

Expression of herpes virus entry mediator (HVEM) in the cornea and trigeminal ganglia of normal and HSV-1 infected mice. Curr Eye Res 2009 Oct;34(10):896-904

Date

11/10/2009

Pubmed ID

19895317

DOI

10.3109/02713680903184250

Scopus ID

2-s2.0-70449507068 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

PURPOSE: 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.

MATERIALS AND 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.

Author List

Kovacs SK, Tiwari V, Prandovszky E, Dosa S, Bacsa S, Valyi-Nagy K, Shukla D, Valyi-Nagy T

Author

Sandor K. Kovacs MD Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Cell Line
Cornea
Cricetinae
Female
Gene Expression Regulation
Herpesvirus 1, Human
Humans
Inflammation
Keratitis, Herpetic
Mice
Mice, Inbred BALB C
Receptors, Tumor Necrosis Factor, Member 14
Trigeminal Ganglion
Virus Internalization
Virus Latency
Virus Replication