FIDELITY OF HIV-1 REVERSE-TRANSCRIPTASE
FIDELITY OF HIV-1 REVERSE-TRANSCRIPTASE
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DOI：
10.1126/science.2460924
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发表时间：
1988-11-25
期刊：
影响因子：
56.9
通讯作者：
LOEB, LA
中科院分区：
文献类型：
--
作者：
PRESTON, BD;POIESZ, BJ;LOEB, LA
1型人类免疫缺陷病毒（HIV - 1）表现出广泛的基因变异并经历快速进化。通过三种不同的检测方法在体外DNA聚合过程中对纯化的HIV - 1逆转录酶的保真度进行了测定。来自HIV - 1的逆转录酶在来自噬菌体φX174琥珀3的DNA中引入碱基替换错误，估计频率为1/2000到1/4000。对与单个模板腺嘌呤残基相对的错误掺入率的分析表明，HIV - 1逆转录酶催化核苷酸错配的特异性为A:C >> A:G > A:A。HIV - 1逆转录酶在体外较高的错误率相当于大约每2000到4000个核苷酸中有5到10个错误。这种较高的错误率表明，HIV - 1逆转录酶的错误掺入至少在一定程度上是艾滋病病毒高突变性的原因。错误掺入的特异性可能为抗病毒核苷的系统构建提供基础。
The human immunodeficiency virus type 1 (HIV-1) shows extensive genetic variation and undergoes rapid evolution. The fidelity of purified HIV-1 reverse transcriptase was measured during DNA polymerization in vitro by means of three different assays. Reverse transcriptase from HIV-1 introduced base-substitution errors in DNA from the bacteriophage .phi.X174 amber 3 at estimated frequencies of 1/2000 to 1/4000. Analyses of misincorporation rates opposite a single template adenine residue showed that HIV-1 reverse transcriptase catalyzed nucleotide mismatches with a specificity of A:C >> A:G > A:A. The higher error rate of HIV-1 reverse transcriptase in vitro translates to approximately five to ten error rate suggests that misincorporation by HIV-1 reverse transcriptase is, at least in part, responsible for the hypermutability of the AIDS virus. The specificity of misincorporation may provide a basis for the systematic construction of antiviral nucleosides.