HSV-1 shedding by lontophoresis of 6-hydroxydopamine followed by topical epinephrine.

The development of an animal model for herpes simplex virus (HSV) reactivation is of great importance in studying HSV latency, reactivation, recurrence, and chemotherapy. Epinephrine iontophoresis to the cornea can induce HSV type 1 (HSV-1) ocular shedding from latently infected rabbits. In the present experiment, adrenergic induction of HSV-1 was enhanced by iontophoresis of 6-hydroxydopamine (6-HD) to the rabbit cornea followed by topical epinephrine to the eye. Eye swabs were utilized to determine HSV-1 shedding in the tear film. The combined treatment was performed on selected days during 66 to 292 days (mean 159) postinoculation, resulting in HSV-1 shedding from 100% of the eyes (17/17) within 6 days after the 6-HD treatment. The onset of initial shedding was as early as day 1. The highest frequency (93%) of shedding occurred on day 2. The mean duration of consecutive HSV-1 sheddings was 3.2 days. The importance of prior spontaneous HSV-1 ocular sheddings relative to this induced HSV-1 reactivation system also was demonstrated. Latently infected rabbits that shed virus spontaneously could be induced to shed virus at a much higher frequency and for a longer duration than rabbits that had not shed virus spontaneously. Iontophoresis of 6-HD produced ocular adrenergic supersensitization and with topical epinephrine it induced HSV-1 ocular shedding in 100% of eyes. This new model of induced HSV-1 ocular shedding will be useful for investigation of adrenergic mechanisms that may be involved in HSV reactivation and recurrence.