title: NF-kappaB-dependent control of HIV-1 transcription by the second coding exon of Tat in T cells.
abstract: HIV-1 two-exon transactivator protein (Tat) is a 101-aa protein. We investigated the possible contribution of the extreme C terminus of HIV-1 Tat to maximize nuclear transcription factor NF-kappaB activation, long terminal repeat (LTR) transactivation, and viral replication in T cells. C-terminal deletion and substitution mutants made with the infectious clone HIV-89.6 were assayed for their ability to transactivate NF-kappaB-secreted alkaline phosphatase and HIV-1 LTR-luciferase reporter constructs for low concentrations of Tat. A mutant infectious clone of HIV-89.6 engineered by introducing a stop codon at aa 72 in the Tat open-reading frame (HIVDeltatatexon2) replicated at a significantly lower rate than the wild-type HIV-89.6 in phytohemagglutinin-A/IL-2-stimulated primary peripheral blood lymphocytes. Altogether, our results suggest a critical role for the glutamic acids at positions 92, 94, and 96 or lysines at positions 88, 89, and 90, present in the second encoding Tat exon in activating NF-kappaB, transactivating the HIV-1 LTR and enhancing HIV-1 replication in T cells.
authors: Franche-Comté School of Medicine, Hôpital Saint-Jacques, 2 Place Saint-Jacques, F-25030 Besançon Cedex, France.
authors: Ulrich
authors: U
authors: Mahlknecht
authors: Isabelle
authors: I
authors: Dichamp
authors: Audrey
authors: A
authors: Varin
authors: Carine
authors: C
authors: Van Lint
authors: Georges
authors: G
authors: Herbein
mesh_terms: D000595:Amino Acid Sequence; D005091:Exons; D015756:Genes, tat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D010957:Plasmids; D017354:Point Mutation; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology*; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D016328:NF-kappa B