کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3426026 | 1227311 | 2008 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Effect of transcription peptide inhibitors on HIV-1 replication Effect of transcription peptide inhibitors on HIV-1 replication](/preview/png/3426026.png)
HIV-1 manipulates cellular machineries such as cyclin dependent kinases (cdks) and their cyclin elements, to stimulate virus production and maintain latent infection. Specifically, the HIV-1 viral protein Tat increases viral transcription by binding to the TAR promoter element. This binding event is mediated by the phosphorylation of Pol II by complexes such as cdk9/Cyclin T and cdk2/Cyclin E. Recent studies have shown that a Tat 41/44 peptide derivative prevents the loading of cdk2 onto the HIV-1 promoter, inhibiting gene expression and replication. Here we show that Tat peptide analogs computationally designed to dock at the cyclin binding site of cdk2 have the ability to bind to cdk2 and inhibit the association of cdk2 with the HIV promoter. Specifically, the peptide LAALS dissociated the complex and decreased kinase activity in vitro. We also describe our novel small animal model which utilizes humanized Rag2−/−γc−/− mice. This small peptide inhibitor induces a decrease in HIV-1 viral transcription in vitro and minimizes viral loads in vivo.
Journal: Virology - Volume 376, Issue 2, 5 July 2008, Pages 308–322