IN-VIVO EPINEPHRINE REACTIVATION OF OCULAR HERPES-SIMPLEX VIRUS TYPE-1 IN THE RABBIT IS CORRELATED TO A 370-BASE-PAIR REGION LOCATED BETWEEN THE PROMOTER AND THE 5' END OF THE 2.0-KILOBASE LATENCY-ASSOCIATED TRANSCRIPT

A rabbit ocular model of epinephrine-induced herpes simplex virus type 1 reactivation was employed to study the effect of a deletion in the latency-associated transcript domain. A viral construct derived from 1 7Syn(+), designated 17 Delta Sty, has a deletion of 370 nucleotides be tween genomic positions 118880 and 119250, 17 Delta Sty has been shown to reactivate with wild-type virus kinetics from explants of trigemin al ganglia from latently infected mice. To determine the behavior of t his mutant in an in vivo, inducible reactivation system, rabbit cornea s were infected with 17Syn(+), 17 Delta Sty, or its rescuant, 17 Delta Sty-Res. After viral latency was established, transcorneal epinephrin e iontophoresis was performed. The rabbits latently infected with 17 D elta Sty exhibited a significantly reduced ability to undergo adrenerg ically induced reactivation, i.e., viral shedding in the tears, compar ed with rabbits infected with either 17Syn(+) or 17 Delta Sty-Res. How ever, quantitative PCR demonstrated similar numbers of viral genomes i n the trigeminal ganglia from rabbits latently infected with all three viruses, and all three viruses reactivated in vitro with wild-type ki netics in an explant cocultivation assay. These studies indicate that the 370-bp region deleted in the 17 Delta Sty construct plays a role i n epinephrine-induced reactivation.