Borna disease (BD) is an infectious neurologic disease characterized by profound behavioral disturbances and the accumulation of specific antigens in limbic system neurons. Though BD was originally described in horses, its host range includes birds, sheep and primates. Antibodies to BD antigens have been described in patients with bipolar depression and in patients with AIDS-encephalopathy. Thus, BD may be important not only as a model for virus-induced behavioral disorders but also because the BD agent may be a human pathogen. We have recently cloned cDNAs encoded by the BD agent and have used these cDNAs as probes to characterize the BD agent. Our data indicates that the BD agent is a single-strand, negative-sense RNA virus with a genome of 8.5 kb encoding two major mRNAs of 2.1 kb and 0.8 kb. Cell-fractionation experiments showed that the 2.1 kb and 0.8 kb RNAs are cytoplasmic; in contrast, the 8.5 kb RNA is nucleus-associated. This project will have two complementary goals; 1. to continue our studies in the molecular biology of the BD agent; 2. to use our molecular probes for the BD agent to ask whether BD can be implicated in selected human neuropsychiatric diseases.