NF-KAPPA-B ACTIVATES THE HIV PROMOTER IN NEURONS

Human immunodeficiency virus (HIV) infection of the brain leads to mas sive neuronal damage, resulting in the AIDS (acquired immunodeficiency syndrome) dementia complex (ADC). A recent study using transgenic mic e indicates that neurons possess transcription factors capable of acti vating the HIV promoter. To identify these, we transfected two types o f primary cultures of rat neurons with HIV promoter-reporter gene cons tructs. The two chiB regulatory sites in the HIV long terminal repeat (LTR) are shown to be essential for strong promoter activity. Two prot eins present in neurons, BETA and an NF-chiB-like protein, can bind th e chiB sites. These proteins are shown to belong to distinct families of transcription factors. Mutation analysis and transfection of a domi nant negative NF-chiB mutant, indicate that the neuronal NF-chiB-like activity mediates HIV promoter activation. cDNA cloning, biochemical a nd immunological analyses indicate that neuronal NF-chiB is similar to NF-chiB of other tissues. Transfections of primary neuron cultures wi th an HIV promoter-beta-galactosidase construct show that within these cultures, neurons are indeed the cells that highly activate the HIV p romoter. Thus, analogous to the situation in T-lymphocytes and macroph ages, NF-chiB is an activator of HIV transcription in neurons.