title: Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat.
abstract: The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes. Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B. The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-kappa B from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity. The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed.
authors.affiliation: Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: J P
authors.initials: JP
authors.lastname: Taylor
authors.forename: R J
authors.initials: RJ
authors.lastname: Pomerantz
authors.forename: G V
authors.initials: GV
authors.lastname: Raj
authors.forename: F
authors.initials: F
authors.lastname: Kashanchi
authors.forename: J N
authors.initials: JN
authors.lastname: Brady
authors.forename: S
authors.initials: S
authors.lastname: Amini
authors.forename: K
authors.initials: K
authors.lastname: Khalili
mesh_terms: D001253:Astrocytes / Q000378:metabolism / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002628:Chemoreceptor Cells; D004279:DNA, Viral / Q000235:genetics; D029968:Escherichia coli Proteins; D015696:Gene Products, tat / Q000235:genetics; D016322:HIV Enhancer; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000378:metabolism / Q000382:microbiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D001426:Bacterial Proteins; D004279:DNA, Viral; D029968:Escherichia coli Proteins; D015696:Gene Products, tat; D008565:Membrane Proteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; D054322:tat Gene Products, Human Immunodeficiency Virus