HSV-1 migration in latently infected and naive rabbits after penetrating keratoplasty

PURPOSE. To investigate the migration of herpes simplex virus type 1 (HSV-1 ) between Intently infected and naive corneal tissues and trigeminal gangli on (TG) in rabbits after penetrating keratoplasty (PKP) and transcorneal ep inephrine iontophoresis. METHODS. Two mutants, genetically constructed from HSV-1 strain 17syn(+), w ere used to inoculate rabbit corneas: 17 Delta Pst, a latency associated tr anscript (WT) negative, low-reactivating virus and 17Pr, a high-reactivatin g, LAT-positive rescuant of 17 Delta Pst. Latently infected rabbits were gi ven corneal allografts from naive rabbits, and naive rabbits received graft s from latently infected rabbits. Ninety days after PKP, groups of the tran splanted rabbits were induced to reactivate by transcorneal epinephrine ion tophoresis, but others were not induced. Viral shedding was monitored by te ar film cultures. Rabbits were killed 5 days after iontophoresis. Transplan ted grafts, recipient corneal rims, and corresponding TG were obtained. Nuc leic acids were extracted and amplified for detection of HSV-1 DNA and vira l gene transcription. RESULTS. In naive rabbits receiving grafts transplanted from rabbits latent ly infected with 17Pr (LAT(+)), 3 of 6 corneal rims contained HSV DNA after induction. In contrast, none of the 5 corneal rims from naive rabbits rece iving grafts from rabbits Intent with 17 Delta Pst (LAT(-)) contained viral DNA. Viral DNA and gene transcripts were detected in 2 of G TG from naive rabbits that received grafts from 17Pr (LAT(+)) latently infected rabbits, in recipient corneal rims and TG of Intently infected rabbits receiving gra fts from naive rabbits, viral DNA concentration was significantly greater w ith induced reactivation, compared with the results in noninduced rabbits. The amount of viral DNA in naive grafts transplanted into 17Pr (LAT(+)) lat ently infected rabbits was significantly higher with induction than without induction (P = 0.018). More viral DNA and viral gene transcripts were foun d in tissues from rabbits latently infected with 17Pr (LAT(+)) than in rabb its latently infected with 17 Delta Pst (LAT(-)). CONCLUSIONS. Corneas from latently infected rabbits contain HSV-1 DNA that can replicate after induc ed reactivation Viral migration can occur in both anterograde and retrograd e directions between the transplanted graft and the recipient corneal rim a nd TG. The LAT negative HSV-1 construct 17 Delta Pst has a significantly re duced ability to replicate and migrate.