Role of HIV-1 Nef expression in activation pathways in CD4+ T cells.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Role of HIV-1 Nef expression in activation pathways in CD4+ T cells.

AIDS Res Hum Retroviruses. 1994 May;10(5):523-7. Unique Identifier : AIDSLINE MED/95000924
Carreer R; Groux H; Ameisen JC; Capron A; Centre d'Immunologie et de Biologie Parasitaire, Institut Pasteur; de Lille, France.

Abstract: 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.

Keywords: Base Sequence Cell Line CD4-Positive T-Lymphocytes/*IMMUNOLOGY/*MICROBIOLOGY DNA Probes/GENETICS Gene Expression Regulation, Viral Gene Products, nef/*GENETICS/*IMMUNOLOGY/METABOLISM Genes, nef Guanosine Triphosphate/METABOLISM Human HIV Long Terminal Repeat HIV-1/*GENETICS/*IMMUNOLOGY/METABOLISM Lymphocyte Transformation Lymphokines/BIOSYNTHESIS Molecular Sequence Data NF-kappa B/BIOSYNTHESIS/GENETICS Phosphorylation Transcription Factor AP-1/BIOSYNTHESIS/GENETICS Transfection JOURNAL ARTICLE
950130
M9510845

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