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The Role of Nucleotide Excision by Reverse Transcriptase in HIV Drug Resistance
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, P.O. Box 016129, Miami, FL 33101-6129, USA
* Author to whom correspondence should be addressed.
Received: 10 December 2009; in revised form: 15 January 2010 / Accepted: 25 January 2010 / Published: 28 January 2010
Abstract: Nucleoside reverse transcriptase (RT) inhibitors of HIV block viral replication through the ability of HIV RT to incorporate chain-terminating nucleotide analogs during viral DNA synthesis. Once incorporated, the chain-terminating residue must be removed before DNA synthesis can continue. Removal can be accomplished by the excision activity of HIV RT, which catalyzes the transfer of the 3'-terminal residue on the blocked DNA chain to an acceptor substrate, probably ATP in most infected cells. Mutations of RT that enhance excision activity are the most common cause of resistance to 3'-azido-3'-deoxythymidine (AZT) and exhibit low-level cross-resistance to most other nucleoside RT inhibitors. The resistance to AZT is suppressed by a number of additional mutations in RT, most of which were identified because they conferred resistance to other RT inhibitors. Here we review current understanding of the biochemical mechanisms responsible for increased or decreased excision activity due to these mutations.
Keywords: reverse transcriptase; HIV; antiviral drug resistance; AZT resistance; nucleotide excision; NRTIs; suppression of drug resistance; foscarnet
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MDPI and ACS Style
Acosta-Hoyos, A.J.; Scott, W.A. The Role of Nucleotide Excision by Reverse Transcriptase in HIV Drug Resistance. Viruses 2010, 2, 372-394.
Acosta-Hoyos AJ, Scott WA. The Role of Nucleotide Excision by Reverse Transcriptase in HIV Drug Resistance. Viruses. 2010; 2(2):372-394.
Acosta-Hoyos, Antonio J.; Scott, Walter A. 2010. "The Role of Nucleotide Excision by Reverse Transcriptase in HIV Drug Resistance." Viruses 2, no. 2: 372-394.