Medcrave- The Water Salinization

Online, July 1, 2014 (Newswire.com) - Abstract:-

The human immunodeficiency virus type1 (HIV-1) promoter, the long terminal repeat (LTR), is central to regulating many aspects of viral life cycle dynamics. After viral integration into the host genome, the interactions of host and viral factors with the regulatory elements in the LTR govern viral gene expression, contributing to formation of either a productive transcriptional state or an inactive one. The molecular architecture of the LTR, especially due to the nucleosomal packaging, presents DNA binding elements to cellular transcription factors not only to sites that are upstream of the transcriptional start site but also to regions of the promoter that are downstream of the start site. The importance of the downstream sites has been appreciated specifically in imposing a fine-tuning on the tightly regulated process of gene expression under the control of HIV-1 LTR. This report provides a comprehensive review of the HIV-1 LTR interactions with the transcription factors in the downstream region and summarizes the functional impact of these events on viral gene expression.

Journal of Human Virology & Retrovirology

Medcrave, Medcrave

Keywords: HIV-1; LTR; Transcription factor binding sites

Abbreviations:-

HIV-1: Human Immunodeficiency Virus Type 1;

LTR: Long Terminal Repeat;

C/EBP: CCAAT/Enhancer Binding Protein;

ATF/CREB: Activating Transcription Factor/Cyclic AMP Response Element Binding;

TFBSs: Transcription Factor Binding Sites;

NFAT: Nuclear Factor For Activated T Cells;

DSE: Downstream Sequence Element;

DBF: Downstream Binding Factor;

GLS: Gag Leader Sequence;

EMSA: Electrophoretic Mobility Shift Assays;

TAR: Trans Activation Response;

TPA/PMA-responsive element: Tetra decanoyl phorbol 13-Acetate Responder Element or Phorbol Ester-Responsive Element;

VPA: Valproic Acid;

SAHA: Suberoyl Anilide Hydroxamic Acid;

CNAC: Comprehensive Neuro AIDS Core Center

Introduction:-

Human immunodeficiency virus type 1 (HIV-1) RNA and protein expression relies heavily on interaction of host cellular transcription factors and viral factors with cis-acting regulatory elements within the HIV-1 promoter or long terminal repeat (LTR) (reviewed in [1-3]). The HIV-1 LTR is divided into three regions: unique 3' (U3), repeat (R), and unique 5' (U5) (Figure1). Many cis-acting regulatory elements located upstream of the transcriptional start site (designated+1) have been identified as modulators of HIV-1 proviral gene expression. These elements contain the core promoter region: three Sp1 sites and TATA box; the enhancer region, which includes two nuclear factor-κB sites; and the modulatory region, which includes three CCAAT/enhancer binding protein (C/EBP) sites, the activating transcription factor/cyclic AMP response element binding (ATF/CREB) region, and upstream stimulatory factor (reviewed in [4-6]).

Like the transcription factor binding sites (TFBSs) located upstream of the transcriptional start site, TFBSs present downstream have been shown to act in the process of transcriptional regulation. Such sequences have been reported in both TATA-containing and TATA-less promoters from viral promoters to Drosophila core promoters [7-11]. The HIV-1 LTR contains several important downstream regulatory TFBSs including AP-1 motifs, an AP-3-like (AP-3L) motif, C/EBP/NFAT (nuclear factor for activated T cells) downstream binding site (DS3), two downstream sequence element (DSE) sites, one downstream binding factor (DBF-1), and two Sp1 sites in the U5 and gag leader sequence (GLS) region [5,12-17]. It is also important to note that the nucleotide sequences of some of the aforementioned sites, including AP-3L, DBF-1, Sp1, and C/EBP/NFAT, are well conserved in different HIV-1 isolates, even across different subtypes, which indicates that these sites are important in HIV-1 transcription and replication [12,14]. Such downstream sequences that influence gene expression in HIV have also been shown to be well conserved in some plant viruses including rice tungro bacilliform virus [18], where they modulate the level of RNA pol II processivity and HSV-1 where they are required for late viral gene expression [19]. This review summarizes the well-established downstream TFBSs in the HIV-1 LTR and also describes their functional importance in the highly regulated process of HIV-1 transcription (Table 1). Most studies that have been cited herein utilized electrophoretic mobility shift assays (EMSA) and in vitro foot printing to establish binding site phenotypes and transient expression systems to define the functional role of the downstream TFBSs. This review does not discuss one of the important functional regions, the trans activation response (TAR) element found within the R (nt+1 to +60) region because this element has been extensively reviewed recently [5,20].