Chronic viral infections in the CNS can cause progressive neurologic disorders associated with diverse pathologic manifestations. These findings led to the hypothesis that viruses can contribute to human mental diseases of unknown etiology. Determining the mechanisms by which viruses persist in the CNS and affect brain function is of paramount importance both in biomedical and basic brain research. Both viruses persist in the CNS and cause cognitive and behavioral abnormalities. We are using a combination of animal models and tissue culture systems to investigate the mechanisms whereby persistence of BDV and LCMV in the CNS lead to altered synaptic function, neurochemical disturbances, and impaired cognitive and memory functions without overt damage to brain structures.
Astrocytes play a central role in maintaining brain homeostasis.
BDV persistence in the CNS causes a chronic and prominent astrocytosis. Hence, we are investigating the effects of BDV on astrocyte function. We are also examining the cellular and molecular bases that underlie BDV-induced degeneration of the hippocampal dentate gyrus and alterations in cerebellar development. With this approach, we can identify virally induced alterations in mRNA expression whether or not the mRNA has been discovered previously. BDV has a negative-stranded RNA genome with an organization characteristic of Mononegavirales.