ACTIVATION OF THE HIV-1 LONG TERMINAL REPEAT BY NERVE GROWTH-FACTOR

The brain is an important target for the human immunodeficiency virus type 1 (HIV-1), We show here that nerve growth factor (NGF), which ind uces neuronal differentiation and survival, causes a strong activation of the HIV-1 long terminal repeat by a Ras/Raf-dependent mechanism in PC12 cells, Mutation of the kappa B sequences contained whithin the l ong terminal repeat reduces NGF-mediated stimulation, NGF does not act ivate NF-kappa B in PC12 cells, but rather increases binding of other nuclear factors to the kappa B sequences. Furthermore, a nuclear recep tor response element contributes to the stimulatory effect of NGF, The retinoids receptors have been identified as components of the nuclear binding to the nuclear receptor response element in NGF-treated PC12 cells. These results reveal the importance of neurotrophins and nuclea r receptor signaling pathways as specific activators of HIV-1 gene exp ression in neural cells.