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,
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.