Inhibition of HIV-1 virus replication using small soluble Tat peptides.
Virology(2006)
Abstract
Although the introduction of highly active antiretroviral therapy (HAART) has led to a significant reduction in AIDS-related morbidity and mortality, unfortunately, many patients discontinue their initial HAART regimen, resulting in development of viral resistance. During HIV infection, the viral activator Tat is needed for viral progeny formation, and the basic and core domains of Tat are the most conserved parts of the protein. Here, we show that a Tat 41/44 peptide from the core domain can inhibit HIV-1 gene expression and replication. The peptides are not toxic to cells and target the Cdk2/Cyclin E complex, inhibiting the phosphorylation of serine 5 of RNAPII. Using the Cdk2 X-ray crystallography structure, we found that the low-energy wild-type peptides could bind to the ATP binding pocket, whereas the mutant peptide bound to the Cdk2 interface. Finally, we show that these peptides do not allow loading of the catalytic domain of the cdk/cyclin complex onto the HIV-1 promoter in vivo.
MoreTranslated text
Key words
HIV,Cyclin-dependent kinase,Tat,Peptide inhibitor,Transcription,Cell cycle,Computer modeling,PBMC
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined