Preston B D, Poiesz B J, Loeb L A
Department of Pathology, University of Washington, Seattle 98195.
Science. 1988 Nov 25;242(4882):1168-71. doi: 10.1126/science.2460924.
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 amber3 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 much greater than A:G greater than A:A. The high error rate of HIV-1 reverse transcriptase in vitro translates to approximately five to ten errors per HIV-1 genome per round of replication in vivo. This high 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.
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。通过三种不同的测定方法，在体外DNA聚合过程中测量了纯化的HIV-1逆转录酶的保真度。来自HIV-1的逆转录酶在噬菌体φX174琥珀3型的DNA中引入碱基替换错误的估计频率为1/2000至1/4000。对单个模板腺嘌呤残基对面的错配率分析表明，HIV-1逆转录酶催化核苷酸错配的特异性为A:C远大于A:G大于A:A。HIV-1逆转录酶在体外的高错误率转化为体内每轮复制时每个HIV-1基因组约有五到十个错误。这种高错误率表明，HIV-1逆转录酶的错配掺入至少部分地导致了艾滋病病毒的高变异性。错配掺入的特异性可能为抗病毒核苷的系统构建提供基础。
