%0 Journal Article
%T Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency
%A Gillian M. Schiralli Lester
%A Andrew J. Henderson
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/614120
%X Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed. 1. Introduction A critical step in the HIV life cycle is transcriptional regulation of the integrated provirus. Robust transcription assures that sufficient mRNA and genomic RNA are produced for efficient virus assembly and infectivity. Repression of HIV transcription leads to the establishment of HIV latency, which creates repositories for infectious and drug-resistant viruses that reemerge upon treatment failure or interruption [1¨C4]. The existence of long-lived stable HIV reservoirs was demonstrated by the rebound of virus replication following highly active antiretroviral therapy (HAART) interruption [5¨C8]. These latent reservoirs, which include quiescent memory T cells, tissue-resident macrophages [9, 10], and potentially hematopoietic stem cells [11], although this is still controversial [12], represent long-lived subsets of cells with decreased or inactive proviral transcription. In general, studies with chronically and acutely infected cells show that mutations in Tat [13, 14], absence of cellular transcription factors [15¨C18], miRNA machinery [19, 20], and proviral integration into transcriptionally silent sites contribute to postintegration latency [21, 22]. Although there may not be a common mechanism that promotes HIV latency, it is critical to understand the molecular events that establish and maintain latency if strategies to reduce or purge HIV from latent reservoirs are to be devised [9, 23, 24]. HIV transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcriptional elongation, and chromatin organization. How these events are coordinated and their role in HIV latency will be reviewed. In particular, mechanisms that contribute to repressing HIV transcription will be highlighted. 2. LTR and Transcription Factors Although viral accessory proteins, such as Vpr, and putative elements within the HIV
%U http://www.hindawi.com/journals/mbi/2012/614120/