Exploiting Structurally Diverse Nucleoside Analogs as Probes of Reverse Transcription Complexes

Title: Exploiting Structurally Diverse Nucleoside Analogs as Probes of Reverse Transcription Complexes

Volume: 5 Issue: 1

Author(s): Jason W. Rausch and Stuart F. J. Le Grice

Affiliation:

Keywords: central termination sequence (CTS), HIV-1 RT, RNA/DNA hybrid, equine infectious anemia virus (EIAV), Locked Nucleic Acid

Abstract: The emergence of drug-resistant HIV-1 strains presents a challenge for the design of new drugs. Targeting host cell factors involved in the regulation of HIV-1 replication might be one way to overcome the resistance of HIV-1 to anti-viral agents. Our recent studies identified protein phosphatase-1 (PP1) as an important regulator of HIV-1 transcription. Transcription of HIV-1 genes is activated by HIV-1 Tat protein that induces phosphorylation of the Cterminal domain of RNA polymerase-II by CDK9/cyclin T1. We have shown that HIV-1 Tat binds PP1 in vitro; targets PP1 to the nucleus; and that Tat interaction with PP1 is important for HIV-1 transcription. In this review, we discuss two potential targets of PP1 in Tat-induced HIV-1 transcription: the C-terminal domain of RNA polymerase-II and CDK9. We also present a computer model of Tat-PP1 complex that might be useful for future drug design in anti-HIV- 1 therapeutics.

Cite this article as:

Rausch W. Jason and J. Le Grice F. Stuart, Exploiting Structurally Diverse Nucleoside Analogs as Probes of Reverse Transcription Complexes, Current HIV Research 2007; 5 (1) . https://dx.doi.org/10.2174/157016207779316332