Behavior alterations in tree shrews (Tupaia glis, Diard 1820) induced by Borna disease virus

Abstract

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.

Epidemiology and host spectrum of Borna disease virus infections

“…As BDV infects a wide variety of animal species with a predilection for the limbic system, and occasionally induces persistent emotional, cognitive and behavioural alterations in experimental animals, including primates and their ancestors tree shrews (Tupaia glis) (Sprankel et al, 1978;Stitz et al, 1980), the question has arisen of whether the virus could also be a human pathogen and cause neuropsychiatric disorders. The first evidence of human infections was, indeed, reported in 1985: 0.43-12.5 % of patients with diverse psychiatric disorders had BDV antibodies in serum, whereas the seroprevalence in the control group was ,0.5 % (Rott et al, 1985).…”

Detection of Borna disease virus RNA from peripheral blood cells in schizophrenic patients and mental health workers

“…E-mail: cchenȰmail.tcu.edu.tw Received 8 December 1998; revised and accepted 26 April 1999 of BDV infection in the pathogenesis of human mental disorders. [2][3][4][5] Evidence for the possible link between BDV infection and human mental disorders first came from seroepidemiological studies. 6,7 Several research groups have demonstrated a significantly higher seroprevalence rate of anti-BDV antibodies in psychiatric patients than in normal controls.…”

Borna disease virus antibodies and the deficit syndrome of schizophrenia

“…In animal hosts, BDV infection has a breadth of behavioral manifestations, ranging from asymptomatic to subtle changes in social affiliative behavior to fatal meningoencephalitis (Sprankel et al, 1978;Dittrich et al, 1989;Bautista et al, 1995Bautista et al, , 1994. Animal data suggest that BDV is an interesting candidate for an infectious agent in schizophrenia.…”

“…Animal data suggest that BDV is an interesting candidate for an infectious agent in schizophrenia. Infections with BDV can result in behavioral abnormalities in the absence of an inflammatory response (Sprankel et al, 1978;Dittrich et al, 1989;Bautista et al, 1994Bautista et al, , 1995. The limbic system, a site for schizophrenia-associated pathology, is a major target for BDV replication (Narayan et al, 1983;Gosztonyi and Ludwig, 1984;Solbrig et al, 1994) and BDV infection results in early localization to hippocampus and subsequent damage to the dentate gyrus (Carbone et al, 1991).…”