EXTRACELLULAR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT PROTEIN IS ASSOCIATED WITH AN INCREASE IN BOTH NF-KAPPA-B BINDING AND PROTEIN-KINASE-C ACTIVITY IN PRIMARY HUMAN ASTROCYTES

Human immunodeficiency virus type 1 (HIV-1) infection has been associa ted with an increase in the binding of the transcription factor NF-kap pa B to its consensus sequence in the viral promoter, Using cultures o f primary human fetal astrocytes, we show that exogenous HIV-1 Tat pro tein, which has been demonstrated to be released from infected cells, is associated with an increase in the binding of this transcription fa ctor to an HIV-1 long terminal repeat kappa B sequence. This effect oc curs rapidly and is independent of new protein synthesis. We also demo nstrate that extracellular Tat protein is associated with an increase in protein kinase C activity. If Tat functions similarly in other cell types, such findings could relate to some of this protein's previousl y described physiological effects. These effects include Tat's ability to upregulate the synthesis of specific cytokines and to act as a gro wth factor.