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Journal of Virology, September 2000, p. 8159-8165, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Vpr Contains Two Leucine-Rich Helices That Mediate Glucocorticoid Receptor Coactivation Independently of Its Effects on G2 Cell Cycle Arrest

Michael P. Sherman,1,2 Carlos M. C. de Noronha,1 David Pearce,3 and Warner C. Greene1,3,4,*

Gladstone Institute of Virology and Immunology1 and Departments of Medicine,3 Microbiology and Immunology,4 and Hematology and Oncology,2 University of California, San Francisco, California

Received 23 March 2000/Accepted 31 May 2000

Human immunodeficiency virus type 1 (HIV-1) Vpr participates in nuclear targeting of the viral preintegration complex in nondividing cells and induces G2 cell cycle arrest in proliferating cells, which creates an intracellular milieu favorable for viral replication. Vpr also activates the transcription of several promoters and enhancers by a poorly understood mechanism. Vpr enhances glucocorticoid receptor (GR) signaling and may mediate the effects of steroids on HIV replication. More specifically, recombinant Vpr can potentiate virion production from U937 cells, downregulate NF-kappa B induction, and enhance programmed cell death, all effects also mediated by glucocorticoids. Vpr has been proposed to act as a GR coactivator, although other studies suggest that these enhancing effects are merely a consequence of G2 cell cycle arrest. We now demonstrate that Vpr functions as a GR coactivator and that this activity is independent of cell cycle arrest. In addition, we show that the Vpr-induced coactivation requires an intact glucocorticoid response element, that it is dependent on the presence of hormone and the corresponding receptor, and that it is mediated by the two highly conserved leucine-rich domains within Vpr that resemble the GR coactivator signature motif.

* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94141-9100. Phone: (415) 826-3800. Fax: (415) 826-1817. E-mail: wgreene{at}gladstone.ucsf.edu.

Journal of Virology, September 2000, p. 8159-8165, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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