Dementia associated with human immunodeficiency virus (HIV) infection is one of the primary debilitating central nervous system (CNS) symptoms associated with the later stages of the acquired immunodeficiency virus syndrome (AIDS). Microglia are fundamental to the progression of the dementia, as HIV will enter the brain and reside in microglia where the microglia serve as a reservoir for viral replication and progression of HIV-associated dementia (HIVD). The CNS symptoms are perpetuated when microglia are activated upon HIV infection. The result is an unregulated neurotoxic microglial inflammatory response that eventually leads to dementia. Increasing evidence indicates that suppression of viral replication will reduce symptoms of HIVD. This work proposes that inhibition of inflammatory response in microglia will reduce the replication of HIV in the brain, which would minimize the neuronal death. Thus, this study will investigate whether novel opiate compounds shown to reduce microglia activation at low doses will both reduce microglial inflammatory responses and provide further therapeutic potential by reducing viral replication. The long terminal repeat (LTR) of the HIV promoter will be transfected into microglial cell lines, where the HIV-LTR promoter activity will be used as a model to investigate the mechanisms of viral replication associated with microglial activation. The effect of LPS induced microglial activation on the transactivation of the HIV-LTR promoter will be assessed by luciferase assay. The impact of dynorphin (DYN) opiate peptides such as DYN A (1-17), DYN A (1-8), DYN A (1-5), and DYN A (2-5) on HIV-LTR promoter activity will be investigated. Finally, the intracellular signaling pathways that are modified by the low concentrations of DYN
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