The applicant has recently demonstrated that inoculation of MCMV into the supraciliary space of immunocompetent BALB/c mice results in a retinitis that has some of the same histopathologic features observed in eyes of immunocompromised human patients with CMV retinitis. The first of the proposed experiments will be performed in immunocompetent BALB/c mice. The investigator will use virologic, immunologic and molecular biological techniques to determine the extent and location of virus replication following inoculation of virus into the supraciliary space, sites of viral latency, and the systemic immune response. These experiments will be followed by performance of dose-response experiments to select a dose of virus that results in minimal retinal involvement at the time of initial infection but which produces latency in the retina (and/or in other ocular structures). The applicant then proposes to use various specific (depletion of T cell subsets) and non-specific strategies of immunosuppression to reactivate virus and produce retinitis.
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