Strain specificity of spontaneous and adrenergically induced HSV-1 ocular reactivation in latently infected rabbits

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Abstract
Spontaneous ocular shedding and adrenergic induction of ocular shedding were examined in rabbits infected with ten strains of herpes simplex virus type 1 (HSV-1): McKrae, KOS, F, Rodanus, 17 Syn+, RE, E-43, SC-16, MacIntyre, and CGA-3. All ocular inoculations were with 50 μ1 of HSV-1 with titers between 1-10 × 106 PFU/ml. All corneas, except those that received the McKrae strain, were scarified. Acute ocular infection was determined by slit-lamp biomicroscopy. Dendritic keratitis or geographic ulcers developed in all eyes of all rabbits within 10 days after ocular inoculation. All eyes of all surviving rabbits were swabbed for 20 consecutive days during days 20-39 postinoculation (PI). On PI day 19, no active lesions were present as judged by slit-lamp biomicroscopy. Ocular tear film was collected on a Dacron-tipped swab and placed on primary rabbit kidney cell monolayers. The cell monolayers were monitored for cytopathic effects consistent with HSV-1 infection. Spontaneous HSV-1 shedding was detected in some eyes from all groups of latently infected rabbits, except those infected with CGA-3. Spontaneous shedding (positive swabs/total swabs) of the other nine strains ranged from 0.7% to 15.7%. After PI day 42, the rabbit eyes received 6-hydroxydopamine by iontophoresis, followed for 5 days by topical application of 2% epinephrine. This procedure results in induced HSV-1 ocular shedding for a duration of 3-5 days in rabbits infected with the McKrae strain. In rabbits latently infected with KOS, F, RE, MacIntyre, and CGA-3, no induced HSV-1 shedding was detected. In addition to the McKrae strain, 17 Syn+, E-43, and SC-16 strains could be adrenergically induced to shed virus. All eyes of rabbits latently infected with Rodanus shed virus spontaneously, however, no induction occurred. Co-cultivation of the trigeminal and superior cervical ganglia revealed that all ten strains were present in the latent phase in these neural tissues. For all strains, the frequencies of recovery of latent HSV-1 from the trigeminal and superior cervical ganglia were the same regardless of whether the corresponding eye shed virus or did not shed virus. We conclude that all these strains of HSV-1 develop neural latency at about the same frequency. Furthermore, ocular reactivation is strain-specific and can be separated into an endogenous (spontaneous) and exogenous (induced) event.