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R. D. Dix, Y. Li, H. Chein, S. W. Cousins; Susceptibility to MCMV Retinitis During Progression of Retrovirus-Induced Immunosuppression in Mice: A Summary of Pathogenetic Events. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5136. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
A series of studies were performed to define with some precision the virologic and immunologic events that take place to allow susceptibility to experimental murine cytomegalovirus (MCMV) retinitis in mice during progression of MAIDS, a retrovirus-induced immunodeficiency syndrome.
Groups of C57BL/6 mice at 2, 4, 6, 8, and 12 weeks after retrovirus infection were challenged with MCMV by subretinal inoculation, and MCMV-inoculated eyes were collected and analyzed for virus titers, retinal disease, perforin mRNA levels, and IL-4 mRNA levels at various stages of MAIDS. Normal mice served as controls.
Whereas normal, MAIDS-2, and MAIDS-4 mice were resistant to retinal disease (0%), ~33% of MAIDS-6 mice exhibited MCMV retinitis, and susceptibility increased in MAIDS-8 (~80%) and MAIDS-12 (100%) mice. Increased susceptibility to MCMV retinitis was accompanied by a dramatic increase in ocular MCMV titers and a concomitant decrease in perforin mRNA levels suggesting loss of the perforin cytotoxic pathway at a time when IL-4 mRNA levels increased. Surprisingly, MCMV-inoculated eyes of MAIDS-4 mice harbored high MCMV titers in the absence of retinal disease, and at a level equivalent to that found in MCMV-inoculated eyes of MAIDS-6, MAIDS-8, and MAIDS-12 mice that exhibited retinal necrosis.
We conclude that key events that take place between 2 and 4 weeks after retrovirus infection are pivotal toward allowing increased susceptibility to MCMV retinitis, an early time in the progression of MAIDS that corresponds to changes in cytokine profiles that serve to dampen the perforin cytotoxic pathway and decrease resistance to onset of retinal disease. These findings set the stage for clinical studies designed to measure blood perforin mRNA levels in HIV/AIDS patients and other immunosuppressed patient populations as a possible predictor for increased susceptibility to onset of cytomegalovirus retinal disease.
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