SPREAD OF HSV-1 TO THE SUPRACHIASMATIC NUCLEI AND RETINA IN T-CELL DEPLETED BALB C MICE/

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 uni njected 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 t he optic nerve and retina of the injected eye is observed only in athy mic mice or in mice depleted of both CD4(+) and CD8(+) T cells. To det ermine the role of T cells in virus spread, adult female BALB/c mice w ere thymectomized and T cell depleted. Mice were co-injected with the KOS strain of HSV-I and RH116, a thymidine kinase-negative mutant of K OS 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-stai ned, virus-infected cells. A difference in the timing of virus infecti on 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 co ntralateral suprachiasmatic nucleus was infected two days earlier. Sin ce one route by which virus could infect the retina of the injected ey e is via connections of the contralateral suprachiasmatic nucleus to t he 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 suprachia smatic nucleus followed by spread of virus to the ipsilateral optic ne rve and retina and (b) early HSV-1 infection of the contralateral supr achiasmatic nucleus is prevented by a T cell dependent mechanism. (C) 1997 Elsevier Science B.V.