title: The peri-kappa B site mediates human immunodeficiency virus type 2 enhancer activation in monocytes but not in T cells.
abstract: Human immunodeficiency virus type 2 (HIV-2), like HIV-1, causes AIDS and is associated with AIDS cases primarily in West Africa. HIV-1 and HIV-2 display significant differences in nucleic acid sequence and in the natural history of clinical disease. Consistent with these differences, we have previously demonstrated that the enhancer/promoter region of HIV-2 functions quite differently from that of HIV-1. Whereas activation of the HIV-1 enhancer following T-cell stimulation is mediated largely through binding of the transcription factor NF-kappa B to two adjacent kappa B sites in the HIV-1 long terminal repeat, activation of the HIV-2 enhancer in monocytes and T cells is dependent on four cis-acting elements: a single kappa B site, two purine-rich binding sites, PuB1 and PuB2, and a pets site. We have now identified a novel cis-acting element within the HIV-2 enhancer, immediately upstream of the kappa B site, designated peri-kappa B. This site is conserved among isolates of HIV-2 and the closely related simian immunodeficiency virus, and transfection assays show this site to mediate HIV-2 enhancer activation following stimulation of monocytic but not T-cell lines. This is the first description of an HIV-2 enhancer element which displays such monocyte specificity, and no comparable enhancer element has been clearly defined for HIV-1. While a nuclear factor(s) from both peripheral blood monocytes and T cells binds the peri-kappa B site, electrophoretic mobility shift assays suggest that either a different protein binds to this site in monocytes versus T cells or that the protein recognizing this enhancer element undergoes differential modification in monocytes and T cells, thus supporting the transfection data. Further, while specific constitutive binding to the peri-kappa B site is seen in monocytes, stimulation with phorbol esters induces additional, specific binding. Understanding the monocyte-specific function of the peri-kappa B factor may ultimately provide insight into the different role monocytes and T cells play in HIV pathogenesis.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0642, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Clark
authors.forename: M C
authors.initials: MC
authors.lastname: Hannibal
authors.forename: D M
authors.initials: DM
authors.lastname: Markovitz
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D014407:Tumor Cells, Cultured
chemical_list: D004279:DNA, Viral; D016328:NF-kappa B; D009687:Nuclear Proteins