Volume 3 Supplement 1

2006 International Meeting of The Institute of Human Virology

Open Access

The HIV-1 Vpr and glucocorticoid receptor complex is a gain of function interaction that prevents the nuclear localization of PARP-1

  • Karuppiah Muthumani1,
  • Andrew Y Choo1,
  • Wei-Xing Zong2,
  • Muniswamy Madesh2,
  • Daniel S Hwang1,
  • Arumugam Premkumar3,
  • Craig B Thompson2 and
  • David B Weiner1
Retrovirology20063(Suppl 1):S105

https://doi.org/10.1186/1742-4690-3-S1-S105

Published: 21 December 2006

The Vpr protein of HIV-1 functions as a vital accessory gene by regulating various cellular functions including cell differentiation, apoptosis, NF-κB suppression and cell cycle arrest of the host cell. Several reports have suggested that Vpr complexes with the glucocorticoid receptor (GR), but it remains unclear whether the GR pathway is required for Vpr's effects. Here we report that Vpr utilizes the GR pathway as a recruitment vehicle for the NF-κB coactivating protein Poly(ADP-Ribose) Polymerase-1 (PARP-1). The glucocorticoid receptor interaction with Vpr is both necessary and sufficient to facilitate this interaction by potentiating the formation of a Vpr/GR/PARP-1 complex. The recruitment of PARP-1 by the Vpr/GR complex prevents its nuclear localization, which is necessary for Vpr to suppress NF-κB. The association of GR with PARP-1 is not observed with steroid (glucocorticoid) treatment, suggesting that the GR association with PARP-1 is a gain of function solely attributed to HIV-1 Vpr. These data provide important insight into Vpr biology and its role in HIV pathogenesis.

Authors’ Affiliations

(1)
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine
(2)
Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania School of Medicine
(3)
Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center

Copyright

© Muthumani et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.

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