The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product

Yosef Refaeli, David N. Levy, David B. Weiner

Research output: Contribution to journalArticle

Abstract

The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 15- kDa virion-associated protein that functions as a regulator of cellular processes linked to the HIV life cycle. We report the interaction of a 41- kDa cytosolic viral protein R interacting protein 1 (Rip-1) with Vpr in vitro. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-II-stimulating steroids. Importantly, Vpr and Rip-1 coimmunoprecipitated with the human GR as part of an activated receptor complex. Vpr complementation of a vpr mutant virus was also mimicked by GR- II-stimulating steroids. Vpr and GR-II actions were inhibited by mifepristone, a GR-II pathway inhibitor. Together these data directly link the activity of the vpr gene product to the glucocorticoid steroid pathway and provide a biochemical mechanism for the cellular and viral activity of Vpr, as well as suggest that a unique class of antivirals, which includes mifepristone (RU486), may influence HIV-1 replication.

Original languageEnglish (US)
Pages (from-to)3621-3625
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number8
DOIs
StatePublished - Apr 11 1995

ASJC Scopus subject areas

  • General

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