NF-kappa B-dependent induction of the NF-kappa B p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells

Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7826-30. doi: 10.1073/pnas.89.16.7826.


The molecular mechanisms underlying the sustained nuclear translocation of NF-kappa B observed in U937 monocytic cells chronically infected with human immunodeficiency virus (HIV) were studied. The activity of the promoter regulating the synthesis of the p105 precursor of the NF-kappa B p50 subunit was enhanced in these cells. Deletions in this promoter indicated that this upregulation was mediated through the NF-kappa B- but not the AP-1-binding motif, by bona fide p50/p65 heterodimers. Analysis of cytosolic extracts indicated that NF-kappa B levels were increased in HIV-infected cells. In contrast to the transient NF-kappa B activation induced by phorbol ester, the permanent NF-kappa B translocation induced by HIV infection was not dependent on PKC isoenzymes alpha and beta as shown by the use of a specific inhibitor (GF 109203X). These observations indicate that during chronic HIV infection of U937 cells, continuous NF-kappa B (p50/p65) translocation results in p105 promoter upregulation with subsequent cytosolic NF-kappa B accumulation, ready for further translocation. This HIV-mediated mechanism results in a self-perpetuating loop of NF-kappa B production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / physiology
  • Cytoplasm / physiology
  • Enhancer Elements, Genetic
  • HIV Long Terminal Repeat*
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • Humans
  • Indoles / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Macromolecular Substances
  • Maleimides / pharmacology
  • Molecular Sequence Data
  • Monocytes
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism*
  • Oligonucleotide Probes
  • Promoter Regions, Genetic* / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic*
  • Virus Replication


  • Indoles
  • Isoenzymes
  • Macromolecular Substances
  • Maleimides
  • NF-kappa B
  • Oligonucleotide Probes
  • Protein Kinase C
  • bisindolylmaleimide I
  • Tetradecanoylphorbol Acetate