HIV TRANSCRIPTIONAL ACTIVATION BY THE ACCESSORY PROTEIN, VPR, IS MEDIATED BY THE P300 COACTIVATOR

The accessory protein, Vpr, is a virion-associated protein that is req uired for HIV-1 replication in macrophages and regulates viral gene ex pression in T cells. Vpr causes arrest of cell cycle progression at G( 2)/M, presumably through its effect on cyclin B1.Cdc2 activity. Here, we show that the ability of Vpr to activate HIV transcription correlat es with its ability to induce G(2)/M growth arrest, and this effect is mediated by the p300 transcriptional coactivator, which promotes coop erative interactions between the Rel A subunit of NF-kappa B and cycli n B1.Cdc2. Vpr cooperates with p300, which regulates NF-kappa B and th e basal transcriptional machinery, to increase HIV gene expression. Si milar effects are seen in the absence of Vpr with a kinase-deficient C dc2, and overexpression of p300 increases levels of HIV Vpr(+) replica tion. Taken together, these data suggest that p300, through its intera ctions with NF-kappa B, basal transcriptional components, and Cdks, is modulated by Vpr and regulates HIV replication, The regulation of p30 0 by Vpr provides a mechanism to enhance viral replication in prolifer ating cells after growth arrest by increasing viral transcription.