We have studied various virologic and immunopathologic processes that occur when viruses replicate in the ocular microenvironment. This project consists of three areas: (1) studies on coronavirus infection in ocular and optic nerve cells; (2) determination of the possible roles of viruses in human diseases; and (3) studies on antiviral therapeutic actions of cytokines and drugs. 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 inflammation. The initial retinal damage is followed by clearance of the virus and progressive retinal destruction, even months after the virus is gone. In addition to morphologic damage, the virus causes a redistribution and reduction in interphotoreceptor retinoid-binding protein (IRBP). These results demonstrate that the virus can induce biochemical and morphological changes in the retina that persist and progress long after the virus is detectable. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. The need for effective drug treatment and prevention of herpes virus and other viral diseases has assumed growing importance. We found that leukoregulin, a naturally occurring immunologic cytokine, increases the antiviral actions of the drug acyclovir. Our findings, which demonstrate that combination immunotherapy and chemotherapy can produce substantial inhibition of herpesvirus replication, provide a rationale for the application of this approach to the treatment of virus infections.
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