Spread of HSV-1 to the suprachiasmatic nuclei and retina in T cell depleted BALB/c mice.

ABSTRACT

Following uniocular anterior chamber inoculation of the KOS strain of HSV-1 in euthymic BALB/c mice, virus spreads from the injected eye to the brain, and from the brain to the optic nerve and retina of the uninjected eye by day 7 post inoculation (p.i.), but the optic nerve and retina of the injected eye are not infected with virus. Infection of the optic nerve and retina of the injected eye is observed only in athymic mice or in mice depleted of both CD4+ and CD8+ T cells. To determine the role of T cells in virus spread, adult female BALB/c mice were thymectomized and T cell depleted. Mice were co-injected with the KOS strain of HSV-1 and RH116, a thymidine kinase-negative mutant of KOS containing the Escherichia coli lac Z gene. Animals were sacrificed on days 3-7 p.i., and the eyes and brains were examined for blue-stained, virus-infected cells. A difference in the timing of virus infection was observed in the area of the suprachiasmatic nuclei only in mice depleted of both CD4+ and CD8+ T cells, and in this group, the contralateral suprachiasmatic nucleus was infected two days earlier. Since one route by which virus could infect the retina of the injected eye is via connections of the contralateral suprachiasmatic nucleus to the ipsilateral optic nerve, these findings suggest that (a) retinitis observed in the injected eyes of mice depleted of both CD4+ and CD8+ T cells results from virus infection of the contralateral suprachiasmatic nucleus followed by spread of virus to the ipsilateral optic nerve and retina and (b) early HSV-1 infection of the contralateral suprachiasmatic nucleus is prevented by a T cell dependent mechanism.