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.
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.
Paya
C V
CV
Unite d'Immunologie Virale, Institut Pasteur, Paris, France.
Ten
R M
RM
Bessia
C
C
Alcami
J
J
Hay
R T
RT
Virelizier
J L
JL
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D004742:Enhancer Elements, Genetic; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D046911:Macromolecular Substances; D008301:Maleimides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014779:Virus Replication
D007211:Indoles; D007527:Isoenzymes; D046911:Macromolecular Substances; D008301:Maleimides; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate