Significance Borna disease virus (BDV) infects a broad range of warmblooded species(mammals and birds) causing neurologic dysfunction. Although controversial, evidence indicates that BDV may be associated with human neuro-psychiatric disorders. Attempts to demonstrate BDV infections in humans through serologic and molecular analysis of peripheral blood samples have produced inconsistent results. Objective We hypothesize that perinatal infections of rhesus macaques will manifest as subtle neurobehavioral and neuropathologic disturbances in a primate counter part to the neonatal rat model of persistent BDV infection. The objective of these pilot studies is to develop a nonhuman primate model of persistent BDV infection , and determine if the clincal, behavioral and neuropathologic sequelae are consistent with human psychiatric disease. Results Intracranial inoculation of BDV in 2 juvenile rhesus macaques resulted in infection and fatal clinical disease at 5 and 8 weeks pi, respectively. Both animals developed the acute, encephalitic form of BDV infection, indicating that animals of this age are already immunololgically mature enough to preclude immunologic tolerance and persistent infection. Both anmals developed strong humeral immune responses to BDV-specific antigens, thus providing valuable primate reagents for refining and validating available serologic tests. In one animal, preliminary PCR assays have detected viral nucleic acids in samples of peripheral blood mononuclear cells. Future Directions To approximate the immune competence of the neonatal rat, intraventricular inoculation of 2 fetuses have been performed in utero, using ultra-sound guided techniques. Pregancies will go to term, and neonates will be monitored for persistent BDV infection. Future experiments will also evaluate the course of BDV infection in neonatal rhesus inoculated intranasally. KEYWORDS borna disease virus, neurologic dysfunction