Exploiting Structurally Diverse Nucleoside Analogs as Probes of Reverse Transcription Complexes

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

Journal Name: Current HIV Research

Volume 5 , Issue 1 , 2007

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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.

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

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Article Details

VOLUME: 5
ISSUE: 1
Year: 2007
Page: [11 - 22]
Pages: 12
DOI: 10.2174/157016207779316332

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