HSV1 latency sites after inoculation in the lip: Assessment of their localization and connections to the eye

PURPOSE. To localize the sites of HSV1 latency in mice after a primary infection induced by injection into the lip and to assess their connection to the eye. METHODS. The SC16 strain of HSV1, or a recombinant virus containing the HSV1 latency-associated transcript (LAT)-promoter driving expression of the LacZ reporter gene, were injected into the left upper lip. Tissues from animals killed at 6, 28, 180, and 720 days postinoculation (dpi) were analyzed for LATs, either by in situ hybridization (ISH) or by identifying LAT-promoter-driven transgene expression. HSV1 antigens were detected by immunochemistry. RESULTS. At 28 dpi, all the neurologic structures that were acutely infected at 6 dpi exhibited a pattern of virus gene expression consistent with HSV1 latency-that is, LATs with no detectable HSV1 antigens. LAT staining differed among structures: intense and widespread within trigeminal neurons, intermediate within the sympathetic intermediolateral cell group of the spinal cord and the facial motor nucleus, and weak in other sites. Long-term expression of LATs (positive at 180 and 720 days) was observed only in tissues where the staining was intense or intermediate at 28 dpi. CONCLUSIONS. After inoculation into the upper lip of mice, HSV1 established latency in several nervous system structures that have direct or indirect connections with ocular tissues. These results suggest that after an oral primary infection, the most frequent in humans, HSV1 may establish latency in several sites connected to the eye and may finally result in herpetic ocular disease involving the cornea, the iris, or even the retina.