Behavioral Disease in Rats Caused by Immunopathological Responses to Persistent Borna Virus in the Brain

Abstract

Borna virus replicated persistently in the brains of rats, causing frenzied and apathetic behavioral states in sequence but no mortality. The transient frenzied behavior was caused by an immune-mediated, cytolytic, encephalitic response that was unexpectedly self-limiting. Cessation of active pathological processes coincided with the onset of the passive phase of the disease. This study thus demonstrates suppression of virus-specific inflammation despite continuous viral replication and describes a new mechanism by which chronic encephalitis may become established.

Staggering disease in cats: isolation and characterization of the feline Borna disease virus

“…Borna disease (BD) is a neurological syndrome that results from a persistent virus infection of the central nervous system (CNS) (Ludwig et al, 1988), previously reported in horses, sheep and a broad range of experimentally infected animals (Nicolau & Galloway, 1928;Narayan et al, 1983;Ludwig et al, 1985). *Author for correspondence.…”

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

“…Clearance of BDV is generally not observed after experimental infection of various animal species, including the wellstudied rat model (44,64). Due to the insufficiency of available intravitam diagnostic methods, it is unclear whether some infected animals are temporarily replicating the virus before clearing it again (63).…”

Borna disease virus antibodies and the deficit syndrome of schizophrenia

“…O'Donnell and Grace (O'Donnell and Grace, 1995) have proposed and validated a model in which the hippocampus plays a central role in modulating (gating) prefrontal cortex-nucleus accumbens interactions such that hippocampal damage leads to hypofrontality and a hypodopaminergic state. BDV shows a predilection to infect areas in the mesocorticolimbic dopamine system (Narayan et al, 1983;Solbrig et al, 1994Solbrig et al, , 1996a. BDV infection also is specifically associated with hippocampal damage in that, with or without inflammation, infection leads to a marked loss of hippocampal neurons (Narayan et al, 1983;Carbone et al, 1991Carbone et al, , 1996.…”

“…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). BDV infection also results in abnormalities in agonist sensitivity, transmitter depletion, and receptor binding in the dopamine system (Solbrig et al, 1994(Solbrig et al, , 1996a.…”