HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF PROTEIN DOWN-REGULATES TRANSCRIPTION FACTORS NF-KAPPA-B AND AP-1 IN HUMAN T-CELLS IN-VITRO AFTER T-CELL RECEPTOR STIMULATION

Human immunodeficiency virus type 1 (HIV-1) negative factor (Nef) has been shown to down-regulate the transcription factors NF-KB and AP-1 in vitro. To define the mechanism of action of the Nef protein, the signal transduction pathways,which may be affected in T cells by constitutive expression of the nef gene were examined. Stimulation of T cells with tumor necrosis factor, interleukin-l, or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene. On the other hand, stimulation of T cells by mitogens or antibodies to the T-cell receptor (TCR)-CD3 complex: resulted in the down-regulation of transcriptional factors NF-KB and AP-I in cells expressing the nef gene compared with cells not expressing the nef gene. Because the Nef protein does not affect the surface expression of the CD3-TCR complex, we conclude that the Nef protein down-regulates the transcriptional factors NF-KB and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway.