Borna Disease Virus and the Brain

BORNA

DISEASE VIRUS AND THE BRAIN

de la Torre,

J.C.*, D. Gonzalez-Dunia, C. Sauder, M. Watanabe, B Cubitt, K.

Ikuta and E. Masliah. The Scripps Research Institute, La Jolla,

CA

Epidemiological and clinical

findings, together with virological studies indicate that viruses

can persist in the central nervous system (CNS) and contribute to

progressive neurological disorders that are associated with

diverse pathological findings. Non-lytic persistent viruses cause

both subtle changes in neuronal organization and disturbances in

brain cell functions which can perturb CNS homeostasis and lead

impaired brain function in the absence of overt structural

damage. These findings had led to the hypothesis that viruses can

contribute to human mental disorders of unknown etiology.

Therefore, the interest in identifying relevant infectious

agents, and understanding the mechanisms by which viruses persist

in the CNS and interfere with brain function.

Borna disease virus (BDV) causes

central nervous system (CNS) disease in several vertebrate

species which is manifested by behavioral abnormalities that

depend on both host and viral factors. BDV is the prototype of a

new group of nonsegmented negative-stranded (NNS) RNA animal

viruses. BDV provides an important model to study viral

persistence in the CNS. Evidence indicates that the host range

and geographic distribution of BDV is wider than previously

thought. There is serological and molecular data supporting that

BDV can infect humans, and may be associated with certain

neuropsychiatric disorders. BDV antigen and RNA have been

detected in the CNS of individuals with neuropsychiatric

disorders, and infectious virus isolated from autopsy brain

material of a schizophrenic patient.

We will present evidence that BDV

can disturb synaptic function and cause altered cytokine

expression by CNS resident cells. These findings on BDV-cell

interactions in the CNS illustrate possible mechanisms whereby

nonlytic neurotropic viruses may affect brain function in the

absence of the classic hallmarks of inflammation and cytolysis.