Our studies of various virologic and immunopathologic processes that occur when viruses and parasites replicate in the ocular microenvironment comprise five areas: (1) virus-induced retinal degenerative processes; (2) the possible roles of viruses in human diseases; (3) molecular diagnosis and pathogenesis of cytomegalovirus (CMV) infections in man; (4) Varicella-zoster virus (VZV) infections of the retina; and (5) Toxoplasma gondii infections of the retina. We have established that murine coronavirus can induce ocular disease and may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild retinal vascular inflammation. Initial retinal damage is followed by the clearance of infectious virus and progressive retinal degeneration. The retinal degenerative phase of this disease has a persistent virus component, an immune component, and a genetic component. The persistent phase of the virus infection was documented by using in situ hybridization. Sixty days after inoculation, the infectious virus was absent, but viral RNA was present within the retina and retinal pigment epithelium (RPE). This is the first retinal model to demonstrate a virus-induced degeneration, viral persistence, a genetic predisposition to virus-induced tissue damage, and a virus-triggered autoimmune response. Human CMV is a herpesvirus that is a major cause of blindness in children born with congenital infections and in immunocompromised individuals. It is difficult to study CMV latency in man. Therefore, cell culture models of CMV replication and latency may provide insight into a rationale for alternative treatment modalities. We identified that CMV replicates in human RPE cells. However, there are a number of distinct differences in virus replication in RPE cells in comparison with human fibroblasts. Virus replication in RPE cells is atypically slow. In addition, the permissive infection in RPE cells consists of a prolonged period of virus production in the absence of cytopathology. Moreover, characterization of viral protein expression indicated that there was an altered pattern of CMV IE proteins expressed in RPE cells. These alterations in CMV IE gene products may indicate the existence of positive or negative nuclear transcription factors within infected RPE cells. These may be critical variables in viral persistence and viral activation within the retina.
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