Transcription of the integrated HIV provirus is subject to regulation by chromatin organization and must employ host cell transcription factors and chromatin modifying complexes to promote the formation of latency, and then reverse this process to replicate in response to T cell activation. The repressed latent HIV-1 proviral 5' LTR is organized into a defined structure where two de-acetylated and positioned nucleosomes flank the enhancer region, presumably imposing a block to transcriptional initiation and elongation. LTR-associated nucleosomes undergo further histone H3 K9 trimethylation, to cause silencing by recruitment of HP1. In this article, we review current understanding of how the transcriptionally silenced provirus might be established through the function of transcription factors that bind conserved cis-elements, including SP1, YY1, NF-kappa B, CBF-1 and RBF-2 (USF/TFII-I), and propose mechanisms by which factors bound to the repressed LTR can enable reactivation in response to cell signaling.
