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-kappa B 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-1, 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-kappa B and AP-1 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-kappa B and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway.
Bandres
J C
JC
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Ratner
L
L
D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D015536:Down-Regulation; D015693:Gene Products, nef / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000187:drug effects; D010704:Phorbols / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D015693:Gene Products, nef; D016328:NF-kappa B; D010704:Phorbols; D010835:Phytohemagglutinins; D016755:Proto-Oncogene Proteins c-jun; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D014157:Transcription Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C033085:phorbol