SIV is a lentivirus that closely resembles HIV-1 both genetically and in terms of the disease it produces in macaques. The major objective of the this proposal is to identify the presence, onset and severity of neurobehavioral deficits in ten groups of rhesus macaques infected with molecularly clone strains of SIV and subjected to specific treatment protocols. These treatment protocols are designed to test following hypotheses concerning SIC neuropathogenesis: 1) The development of neurobehavioral deficits in association with SIV infection is dependent on the specific strain of virus and its characteristic cell tropism- lymphocyte tropic (L-tropic) or macrophage tropic (M-tropic) 2). The severity of SIV disease and the length of time form infection to the onset of AIDS is influenced by the vigor of the cell mediated immune response, particularly the response of CD8 lymphocytes. 3) Intense immunological activation of mononuclear cells during the acute phase of infection is necessary for production of functional virus (productive replication) in tissues an for dissemination of virus infected cells into the CNS. 4) Productive replication of virus in brain macrophages requires both the presence of neurovirulent M-tropic virus in the brain and immunologically activated CNS cells, especially brain macrophages. Our studies will examine ten treatment groups of SIV infected monkeys infected with specific aims: 1) to identify cloned SIV, 2) to document the onset and progression of conduction velocity slowing in major motor pathways in infection are correlated with neuronal microscopic pathology in cortical and subcortical areas as measured by quantitative morphometry, and 4) to correlated the occurrence of behavioral deficits with evidence of neuropathology detectable with magnetic resonance imaging (MRI) of the brain. These studies should provide insights regarding a recent finding in HIV infected humans that although all patients with HIV encephalopathy have dementia, surprisingly, about half of patients with dementia do not have encephalopathy. This study is particularly timely in view of the limited number of studies of this type on SIV and its importance as a model of HIV infection in humans.
