Role of HIV-1 Nef expression in activation pathways in CD4+ T cells.
The role of the human immunodeficiency virus (HIV-1) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector. Secretion of IL-2 and TNF-alpha, surface expression of IL-2R, and DNA-binding activity of NF-kappa B and AP-1 (Fos/Jun) complex in response to phorbol myristate acetate, TNF-alpha, or immobilized antibodies to CD3 were monitored. These parameters were not modified by Nef expression in Jurkat cells, whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells. This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition. Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B-binding activity but through the region containing the negative responding elements (NREs). These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations.
Carreer
R
R
Centre d'Immunologie et de Biologie Parasitaire, Institut Pasteur de Lille, France.
Groux
H
H
Ameisen
J C
JC
Capron
A
A
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D002460:Cell Line; D015342:DNA Probes / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015754:Genes, nef; D006160:Guanosine Triphosphate / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus
D015342:DNA Probes; D015693:Gene Products, nef; D008222:Lymphokines; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D054311:nef Gene Products, Human Immunodeficiency Virus; D006160:Guanosine Triphosphate