Murine cytomegalovirus ocular infection in immunocompetent and cyclophosphamide-treated mice. Potentiation of ocular infection by cyclophosphamide.

Conventional virologic and in situ nucleic acid hybridization methods were used to study immunocompetent and immunosuppressed 3-week old BALB/c mice inoculated intravitreally with 10(4) plaque-forming units (pfu) of murine cytomegalovirus (MCMV). Immunocompetent mice experienced a self-limited ocular infection with peak virus titers of 10(3.5) pfu/ml in the retina-choroid fraction on day 4 of infection. Using biotinylated MCMV DNA probes, MCMV DNA was detected in cells of the iris, ciliary body, and rarely, the retina or choroid on days 4 and 7 of infection. With few exceptions, retinal architecture was preserved. By contrast, mice immunosuppressed with cyclophosphamide (200 mg/kg on day 0 and 100 mg/kg on days 5 and 11 after MCMV inoculation) had progressive ocular infection that culminated in a necrotizing retinitis. Virus titers in the retina-choroid fraction rose progressively (nearly 10(5) pfu/ml in cyclophosphamide-treated mice on day 11 versus 10(1.5) pfu/ml in immunocompetent mice). The MCMV DNA was detected in the iris and ciliary body of the immunosuppressed mice on days 4 and 7 and in the retina, on days 7, 11, and 14. On day 14 abundant MCMV DNA was found in most retinal layers, and extensive retinal necrosis was observed. These studies indicate that immunosuppression with cyclophosphamide potentiates MCMV ocular disease in mice, a finding analogous to CMV retinitis in immunosuppressed humans.