HIV Transcriptional Activation by the Accessory Protein, VPR, is Mediated by the p300 Co-Activator

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-04, Vol.95 (9), p.5281-5286
• Main Authors: Felzien, Lisa K., Woffendin, Clive, Hottiger, Michael O., Subbramanian, Ramu A., Cohen, Eric A., Nabel, Gary J.
• Format: Article
• Language: English
• Subjects: 3T3 cells; AIDS/HIV; Antibodies; Biological Sciences; CDC2 Protein Kinase - physiology; Cell Cycle; Cell lines; Cell nucleus; Cellular biology; CREB-Binding Protein; Cyclins; Gene Expression Regulation, Viral; Gene Products, vpr - genetics; HIV; HIV-1 - genetics; Human immunodeficiency virus; Humans; Jurkat Cells; Nuclear Proteins - physiology; Plasmids; Proteins; T lymphocytes; Trans-Activators; Transactivation; Transcription Factors - physiology; Transcription, Genetic; Virus Replication; vpr Gene Products, Human Immunodeficiency Virus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.9.5281

The accessory protein, Vpr, is a virionassociated protein that is required for HIV-1 replication in macrophages and regulates viral gene expression in T cells. Vpr causes arrest of cell cycle progression at G2/M, presumably through its effect on cyclin B1· Cdc2 activity. Here, we show that the ability of Vpr to activate HIV transcription correlates with its ability to induce G2/M growth arrest, and this effect is mediated by the p300 transcriptional coactivator, which promotes cooperative interactions between the Rel A subunit of NF-κ B and cyclin B1· Cdc2. Vpr cooperates with p300, which regulates NF-κ B and the basal transcriptional machinery, to increase HIV gene expression. Similar effects are seen in the absence of Vpr with a kinase-deficient Cdc2, and overexpression of p300 increases levels of HIV Vpr+replication. Taken together, these data suggest that p300, through its interactions with NF-κ B, basal transcriptional components, and Cdks, is modulated by Vpr and regulates HIV replication. The regulation of p300 by Vpr provides a mechanism to enhance viral replication in proliferating cells after growth arrest by increasing viral transcription.