Activation of human immunodeficiency virus type 1 provirus in T-cells and macrophages is associated with induction of inducer-specific NF-kappa B binding proteins.
We have analyzed the limiting factors involved in the induction of human immunodeficiency virus type 1 (HIV-1) provirus expression by tumor necrosis factor-alpha (TNF-alpha), phorbol-12-myristate-13-acetate (PMA), and bryostatin-1 in T-cells (ACH-2) and monocytes (U1). We have demonstrated that, while there is a correlation among the increase of 9.2-kilodalton (kDa) HIV-1 RNA, the increase of viral proteins (p24) in the cells, and the release of HIV-1 virions into the medium, there is no direct correlation between the levels of induced NF-kappa B binding proteins and the expression of HIV-1 provirus. The presence of nuclear NF-kappa B-specific proteins appears to be essential only for the initiation of viral replication, since the HIV-1 transcripts could be detected in TNF-alpha or bryostatin-1-stimulated cells also at later times postinduction, times when no NF-kappa B proteins could be detected in the nucleus. The uv crosslinking of DNA and proteins has shown that TNF-alpha, PMA, and bryostatin-1 induce different sets of NF-kappa B binding proteins with distinct kinetics of binding.
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
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D015152:Blotting, Northern; D015153:Blotting, Western; D054713:Bryostatins; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008264:Macrophages / Q000382:microbiology*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010835:Phytohemagglutinins; D011533:Proviruses / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes / Q000382:microbiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014775:Virus Activation / Q000235:genetics*
D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; D016328:NF-kappa B; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C046785:bryostatin 1; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate