In vivo reactivation of latent murine cytomegalovirus in the eye by immunosuppressive treatment

Abstract

Intravitreal inoculation of 10(3) pfu of murine cytomegalovirus (MCMV) to 3-week-old BALB/c mice resulted in virus isolation from eye homogenates for 2 weeks and from co-cultured specimens of the same eye up to 5 weeks after inoculation, indicating that MCMV in the eye became latent 2 weeks after the virus inoculation. Immunosuppressive treatment with daily intramuscular injections of cyclosporine (40 micrograms/g) and cortisone acetate (125 micrograms/g) 9 weeks after intravitreal MCMV inoculation resulted in isolation of infectious virus from ten of 44 eye homogenates (10 of 22 mice) during a 3-week period, indicating in vivo reactivation of latent ocular MCMV. No virus was isolated from eye homogenates of similarly infected mice with sham immunosuppression (daily intramuscular saline injections), nor was any virus isolated from uninfected eyes with immunosuppressive treatment. Three weeks of daily cyclosporine and cortisone injections depleted L3T4+ cells to 6.0%, Lyt-2+ cells to 20% and anti-MCMV antibody to 10% of untreated mice. The results suggest that the eye can serve as a site of latent MCMV that can be reactivated by immunosuppressive means.