strategies to block hiv transcription focus on small molecule tat inhibitors策略阻止艾滋病毒转录专注于小分子乙抑制剂.pdfVIP

Biology 2012, 1, 668-697; doi:10.3390/biology1030668 OPEN ACCESS biology ISSN 2079-7737 /journal/biology Review Strategies to Block HIV Transcription: Focus on Small Molecule Tat Inhibitors Guillaume Mousseau and Susana Valente * Department of Infectious Diseases, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA; E-Mail: mousseau@ * Author to whom correspondence should be addressed; E-Mail: svalente@; Tel.: +1-561-228-3454; Fax: +1-561-228-2916. Received: 11 October 2012; in revised form: 6 November 2012 / Accepted: 7 November 2012 / Published: 19 November 2012 Abstract: After entry into the target cell, the human immunodeficiency virus type I (HIV) integrates into the host genome and becomes a proviral eukaryotic transcriptional unit. Transcriptional regulation of provirus gene expression is critical for HIV replication. Basal transcription from the integrated HIV promoter is very low in the absence of the HIV transactivator of transcription (Tat) protein and is solely dependent on cellular transcription factors. The 5 terminal region (+1 to +59) of all HIV mRNAs forms an identical stem-bulge-loop structure called the Transactivation Responsive (TAR) element. Once Tat is made, it binds to TAR and drastically activates transcription from the HIV LTR promoter. Mutations in either the Tat protein or TAR sequence usually affect HIV replication, indicat