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Retrovirology  2005 

Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT protein

DOI: 10.1186/1742-4690-2-71

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Abstract:

We synthesized a short peptide named Tat-P, which contained the TAR RNA binding and PTD domains to examine whether the peptide has the potential of inhibiting TAT dependent HIV replication. We investigated the inhibiting effects of Tat-P in vitro using a HIV derived lentiviral vector model. We found that the TAT PTD domain not only efficiently transduced test cells, but also effectively inhibited the production of lentiviral particles in a TAT dependent manner. These results were also supported by data derived from the TAT activated LTR-luciferase expression model and RNA binding assays.Tat-P may become part of a category of anti-HIV drugs that competes with full length TAT proteins to inhibit HIV replication. In addition, this study indicates that the HIV derived lentiviral vector system is a safe and reliable screening method for anti-HIV drugs, especially for those targeting the interaction of TAT and TAR RNAs.The HIV TAT protein is a key regulator of viral replication [1]. Binding of the TAT protein to the TAR element, a 59 nt sequence at the 5' end of nascent RNA, is the first critical step for producing full length HIV RNA. The transcription of HIV RNA from both integrated and non-integrated HIV genome is dependent on TAT protein [2]. Thus, interruption of this TAT-TAR interaction has been considered as a possible way to inhibit HIV replication [3]. TAR RNA decoys have been shown to be able to interfere with the binding of TAT proteins to native TAR elements, thus inhibiting HIV replication [4-6]. However, delivery of oligonucleotides in vivo is not trivial. Conversely, small synthetic substances, or short TAT peptides mimicking the TAT and TAR RNA binding domains have been shown to be promising inhibitors of HIV replication [7,8]. Furthermore, a different fragment of the TAT protein could compete for the binding site of the CXCR4 receptor on T cells and inhibit HIV entry [9]. Recently, several research groups have identified the TAR RNA binding domain of the

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