title: Human immunodeficiency virus type 1 genome activation induced by human T-cell leukemia virus type 1 Tax protein is through cooperation of NF-kappaB and Tat.
abstract: For productive replication of human immunodeficiency virus type 1 (HIV-1) in host cells, the viral genome-encoded transactivator Tat and several cellular transcription factors are required for efficient viral gene transcription. However, it remains unclear how the viral genome initiates transcription before Tat is transcribed or when Tat is at suboptimal levels. Here, we utilized the human T-cell leukemia type 1 Tax protein as a molecular tool to investigate the mechanism of viral gene transcription that initiates the early phase of infection of HIV-1. Tax alone does not significantly increase the activity of HIV-1 long terminal repeat (LTR) in T lymphocytes, but it markedly enhanced the replication of an infectious HIV-1 provirus with a truncated nef gene. This enhancement is preferentially mediated by the cooperation of Tax and Tat which is dependent on TAR and duplicated kappaB cis elements of the HIV-1 LTR as well as the NF-kappaB activation domain of Tax. Furthermore, phorbol myristate acetate and membrane-targeted HIV-1 Nef also enhanced the LTR activity in the presence of Tat in the TAR- and kappaB cis element-dependent manner. These data suggest that activated NF-kappaB can functionally interact with a suboptimal amount of Tat and the HIV-1 LTR for efficient initiation of viral gene transcription.
authors.affiliation: Department of Microbiology and Pediatrics, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Tarnok
authors.forename: W P
authors.initials: WP
authors.lastname: Parks
mesh_terms: D001665:Binding Sites; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism*; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D015696:Gene Products, tat; D016356:Gene Products, tax; D008934:Mitogens; D016328:NF-kappa B; D010835:Phytohemagglutinins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D013755:Tetradecanoylphorbol Acetate