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

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 abili...

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Bibliographic Details
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.9.5281