Reactivation and donor-host transmission of herpes simplex virus after corneal transplantation

PURPOSE: To review our previous studies regarding herpes simplex virus type 1 (HSV-1) corneal latency in the rabbit lamellar keratoplasty (LK) and penetrating keratoplasty (PKP) models. METHODS: Rabbits latently infected with HSV- I received allografts from naive rabbits, and naive rabbits received grafts from rabbits latently infected with HSV-1. In rabbits undergoing LK, viral shedding in tear film and the occurrence of herpetic lesions were investigated for 7 days after operation. In rabbits undergoing PKP, latency-associated transcript (LAT)-positive and -negative HSV- I mutants were used to establish latency. Ninety days after PKP, reactivation of HSV-1 was induced by transcorneal iontophoresis of epinephrine. Viral shedding was then assessed by tear-film swabbing. Donor corneal buttons, recipient corneal rims, and corresponding trigeminal ganglia were analyzed for HSV DNA concentration and viral transcription. RESULTS: In rabbits undergoing LK, the occurrence of positive tear-film cultures and number of days on which corneal epithelial lesions were observed were significantly higher in the operated eyes of latently infected rabbits as compared with controls. In rabbits undergoing PKP, HSV- I could transmit between host and donor tissues both in anterograde and retrograde fashion. LAT-positive virus had a significantly greater ability to transmit. Higher concentrations of HSV DNA detected in cornea and trigeminal ganglia correlated with active viral transcription and higher percentage of viral shedding. CONCLUSION: Corneas from latently infected rabbits contain HSV-1 DNA that can replicate and transmit after induced reactivation. Our studies provide further evidence for corneal latency of this virus.