DEFICITS IN DISCRIMINATED LEARNING REMAIN DESPITE CLEARANCE OF LONG-TERM PERSISTENT VIRAL-INFECTION IN MICE

Mice persistently infected with lymphocytic choriomeningitis virus (LC MV) exhibit impaired learning ability. In this report, we determined w hether clearance of the virus was associated with restoration of behav ioral function. Neonatal Balb/cByJ mice were persistently infected wit h LCMV and tested as adults in a nonconditional spatial discrimination task. The presence of viral proteins in neurons was confirmed immunoh istochemically and infectious virus was quantified in the blood by pla que assay. LCMV-infected adult mice made more errors in a Y-maze avoid ance task compared to sham-inoculated controls. After the initial beha vioral analysis, infected and control mice received a dose of cytotoxi c T-lymphocytes sufficient to clear virus from these mice. Following c omplete clearance of the virus, mice were re-tested in the behavioral task, 5 months after the original test. No reversal of the learning de ficit was seen following viral clearance; mice that had been cleared o f the virus and those that remained persistently infected behaved simi larly. These data indicate that persistent LCMV infection of the CNS l asting up to 7 months results in discriminated learning impairments th at are not reversed by subsequent anti-viral immunocytotherapy.