Acosta-Hoyos Antonio J, Scott Walter A
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, P.O. Box 016129, Miami, FL 33101-6129, USA;
Viruses. 2010 Jan 28;2(2):372-394. doi: 10.3390/v2020372.
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.
HIV的核苷逆转录酶（RT）抑制剂通过HIV RT在病毒DNA合成过程中掺入链终止核苷酸类似物的能力来阻断病毒复制。一旦掺入，在DNA合成能够继续之前，链终止残基必须被去除。去除可以通过HIV RT的切除活性来完成，HIV RT催化被阻断的DNA链上3'-末端残基转移到受体底物上，在大多数受感染细胞中可能是ATP。增强切除活性的RT突变是对3'-叠氮-3'-脱氧胸苷（AZT）耐药的最常见原因，并且对大多数其他核苷RT抑制剂表现出低水平交叉耐药。RT中的一些其他突变可抑制对AZT的耐药性，其中大多数是因为它们赋予了对其他RT抑制剂的耐药性而被鉴定出来的。在这里，我们综述了目前对由于这些突变导致切除活性增加或降低的生化机制的理解。
