Journal article
Effect of transcription peptide inhibitors on HIV-1 replication
Virology (New York, N.Y.), v 376(2), pp 308-322
05 Jul 2008
PMID: 18455747
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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
−/−γ
c
−/− mice. This small peptide inhibitor induces a decrease in HIV-1 viral transcription
in vitro and minimizes viral loads
in vivo.
Metrics
Details
- Title
- Effect of transcription peptide inhibitors on HIV-1 replication
- Creators
- Rachel Van Duyne - Washington University Medical CenterJessica Cardenas - George Washington UniversityRebecca Easley - George Washington UniversityWeilin Wu - George Washington UniversityKylene Kehn-Hall - George Washington UniversityZak Klase - George Washington UniversitySusana Mendez - New York State College of Veterinary MedicineChen Zeng - George Washington UniversityHao Chen - George Washington UniversityMohammed Saifuddin - Eastern Virginia Medical SchoolFatah Kashanchi - George Washington University
- Publication Details
- Virology (New York, N.Y.), v 376(2), pp 308-322
- Publisher
- Elsevier
- Number of pages
- 15
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000256718100007
- Scopus ID
- 2-s2.0-44649186124
- Other Identifier
- 991021903314404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology