title: Suppression of HIV-1 transcription by beta-chemokines RANTES, MIP1-alpha, and MIP-1beta is not mediated by the NFAT-1 enhancer element.
abstract: Soluble factors derived from human CD8+ T-lymphocytes inhibit HIV-1 replication by suppressing transcription from the viral long terminal repeat (LTR), an effect shown to be mediated in part by an NFAT-1 enhancer sequence. We show here that the CD8+ derived beta-chemokines, RANTES, MIP1-alpha, and MIP-1beta, known suppressors of HIV-1 replication in human peripheral blood mononuclear cells, can suppress transcription from the HIV-1 LTR in transient transfection assays in cells of the Jurkat (acute T leukemia) line. Surprisingly, the suppression mediated by these beta-chemokines persisted in the absence of an intact NFAT-1 element, suggesting that there are at least two classes of HIV-1 suppressor factors--NFAT-1-dependent and NFAT-1-independent factors--produced by CD8+ T-lymphocytes.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jhanden@atlas.niaid.nih.gov
authors.forename: J S
authors.initials: JS
authors.lastname: Handen
authors.forename: H F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D019402:Macrophage Inflammatory Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase