SIV-infected rhesus macaques are a model for HIV infection and AIDS dementia complex in humans. This study is directed toward 1) identifying the mechanisms underlying the neuronal complications that result from viral infection of the CNS, manifested in impaired motor and/or cognitive function, and 2) testing of the tolerance and efficacy of CNS-directed antiviral agents. We are studying the sequelae of viral infection of the CNS including the neurobehavioral and neuroimmunological consequences, and examining the role of the brain as a viral reservoir and the dissemination of the virus systemically throughout the course of the disease. This animal model allows us to examine the brains of SIV-infected animals at various stages of disease both with and without CNS impairments at the time of death. We have found an increase in astrogliosis in cortical gray matter of neurologically impaired animals, a correlation in the elevation of the endogenous neurotoxin quinolinic acid with onset of motor impairment, and a correlation of elevated somatostatin mRNA in frontal cortex of animals with impairments in both motor and cognitive function. Testing of the tolerance and efficacy of AZT in rhesus neonates, as a model for perinatal transmission of HIV, has revealed that infusion of this anitviral during and for six months following inoculation results in prolonged survival, a decrease in the systemic and CNS viral burden, and a delay in motor impairments compared to untreated animals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research and Development Contracts (N01)
Project #
N01MH010001-013
Application #
2320705
Study Section
Project Start
1990-11-07
Project End
1995-06-30
Budget Start
1994-11-29
Budget End
1995-06-30
Support Year
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Bioqual, Inc.
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20850