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Archives of Virology

, Volume 150, Issue 1, pp 67–78 | Cite as

HIV-1 Vpr enhances production of receptor of activated NF-κB ligand (RANKL) via potentiation of glucocorticoid receptor activity

  • J. M. Fakruddin
  • J. Laurence
Article

Summary.

The HIV-1 accessory protein Vpr potentiates glucocorticoid (GC)-induced inhibition of a variety of immunologically important cytokines. We report the first instance of synergy between Vpr and GC in induction of a T cell cytokine, one which may underlie a metabolic complication of HIV infection. Accelerated bone resorption is an important complication of HIV disease and its treatment. Receptor of activated NF-κB ligand (RANKL) is the final effector of osteoclast differentiation and bone resorption. It is induced by exogenous GC, a prominent cofactor in bone mineral loss, as well as by elevated levels of endogenous GC, found in many patients with HIV disease. We document Vpr-mediated upregulation of RANKL, the dependence of this effect on GC receptor integrity, its function through a classic GC receptor motif, and its independence from Vpr-mediated G2 cell cycle arrest. These data suggest a positive regulatory role for Vpr in transcriptional control of a cytokine that may be critical to one metabolic complication of HIV.

Keywords

Glucocorticoid Bone Resorption Glucocorticoid Receptor Osteoclast Differentiation Metabolic Complication 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag/Wien 2004

Authors and Affiliations

  • J. M. Fakruddin
    • 1
  • J. Laurence
    • 1
  1. 1.Laboratory for AIDS Virus Research, Department of MedicineWeill Medical College of Cornell UniversityNew YorkU.S.A.

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