The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor

• Published in: The Journal of experimental medicine Vol. 189; no. 1; pp. 51 - 62
• Main Authors: Kino, T, Gragerov, A, Kopp, J B, Stauber, R H, Pavlakis, G N, Chrousos, G P
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 04-01-1999
• Subjects: AIDS/HIV; Cell Line; Dexamethasone - pharmacology; Gene Products, vpr - metabolism; Genes, Reporter - genetics; Glucocorticoids - metabolism; HIV-1 - metabolism; Human immunodeficiency virus 1; Humans; Receptors, Glucocorticoid - metabolism; Transcription Factor TFIID; Transcription Factors, TFII - genetics; Transcription Factors, TFII - immunology; Transcriptional Activation - genetics; Transfection - genetics; Viral Proteins - metabolism; vpr Gene Products, Human Immunodeficiency Virus
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.189.1.51

The HIV-1 virion-associated accessory protein Vpr affects both viral replication and cellular transcription, proliferation, and differentiation. We report that Vpr enhances the activity of glucocorticoids in lymphoid and muscle-derived cell lines by interacting directly with the glucocorticoid receptor and general transcription factors, acting as a coactivator. Vpr contains the signature motif LXXLL also present in cellular nuclear receptor coactivators, such as steroid receptor coactivator 1 and p300/CREB-binding protein, which mediates their interaction with the glucocorticoid and other nuclear hormone receptors. A mutant Vpr molecule with disruption of this coactivator signature motif lost its ability to influence transcription of glucocorticoid-responsive genes and became a dominant-negative inhibitor of Vpr, possibly by retaining its general transcription factor-binding activities. The glucocorticoid coactivator activity of Vpr may contribute to increased tissue glucocorticoid sensitivity in the absence of hypercortisolism and to the pathogenesis of AIDS.