Intracerebral injection of Borna disease virus in tree shrews led to a persistent infection that sometimes resulted in clinical symptoms and/or specific alterations in the animals' behavior. Whereas infective virus in the brain and in the serum antibodies were always present after infection, only some of the animals showed signs of clinical disease and behavior changes. Animals kept in pairs showed especially obvious behavior alterations expressed as an exaggeration of all the components of normal social behavior. The division of the roles between males and females was seriously disturbed. The breeding behavior of females was especially impaired, although no stress factors were given and the animals were obviously in good physical condition. Some females that were maintained solitarily showed considerably exaggerated spontaneous locomotor activities (hyperactivity) 4 weeks after infection, followed by a phase of clinical neurologic symptoms (decline phase), spatial and temporal disorientation, and alterations in comfort behavior. Following a slow recovery the animals remained unusually docile and were much less timid than before infection. A recurrence of the clinical illness is possible, as shown by the occurrence of a second decline phase. All the behavior alterations can be interpreted as a disturbance in the balance of approach and avoidance. In paired animals this imbalance results in interference with normal sociosexual behavior. These alterations indicate that BD preferentially involves the limbic system, an interpretation supported by the results of neuropathologic investigations.

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