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. 1992 Aug 15;89(16):7826–7830. doi: 10.1073/pnas.89.16.7826

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.

C V Paya 1, R M Ten 1, C Bessia 1, J Alcami 1, R T Hay 1, J L Virelizier 1
PMCID: PMC49804  PMID: 1502202

Abstract

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.

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Selected References

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