A HIGHLY DEFECTIVE HIV-1 GROUP-O PROVIRUS - EVIDENCE FOR THE ROLE OF LOCAL SEQUENCE DETERMINANTS IN G-]A HYPERMUTATION DURING NEGATIVE-STRAND VIRAL-DNA SYNTHESIS
A HIGHLY DEFECTIVE HIV-1 GROUP-O PROVIRUS - EVIDENCE FOR THE ROLE OF LOCAL SEQUENCE DETERMINANTS IN G-]A HYPERMUTATION DURING NEGATIVE-STRAND VIRAL-DNA SYNTHESIS
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DOI：
10.1006/viro.1995.1191
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发表时间：
1995-04-20
期刊：
影响因子：
3.7
通讯作者：
CLAVEL, F
中科院分区：
文献类型：
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作者：
BORMAN, AM;QUILLENT, C;CLAVEL, F
将整个超突变的O组HIV-1基因组的env和IN区域中的2350个核苷酸的序列与来自同一分离株的非超突变基因组的等效序列进行比较。几乎 30% 的 G 残基受到 G --> A 转换的影响。正如之前报道的，转变主要发生在 GpA 和 GpG 二核苷酸处，并且明显优先于聚 (G) 片段中 5-近端 G 残基的变化。对超突变位点周围序列的检查显示，当突变位于 GpG 二核苷酸的 5'G 残基时，没有偏差。相反，可以定义 3'G（或所有单个 G 残基）超突变的优选背景。除了优先选择紧邻超突变 3'G 残基下游的 A 残基外，这些位置中的 C 残基代表性不足。观察到的背景与模型非常吻合，其中 G --> A 突变是通过 GpA 二核苷酸的位错诱变和 dTTP 在 GpG 二核苷酸 5' G 处的直接错误掺入的组合而发生的。此外，多聚嘌呤束 (PPT) 中存在的 6 个 G 残基的两次运行都逃脱了超突变，尽管 95% 的 3 个 G 残基运行中至少包含一个 G → A 转换。这一发现表明，具有超突变 PPT 基序的基因组已被选择，并提供了负链 DNA 合成过程中发生超突变的直接证据。 (C) 1995 学术出版社
The sequence of 2350 nucleotides in the env and IN regions of a group O HIV-1 genome which is hypermutated throughout its entirety was compared to the equivalent sequence of a nonhypermutated genome from the same isolate. Almost 30% of G residues were affected by G --> A transitions. As previously reported, transitions occurred mainly at GpA and GpG dinucleotides, with a marked preference for changes of the 5-proximal G residues in poly(G) stretches. Inspection of the sequences around the hypermutation sites revealed no bias when the mutation was at the 5' G residue of a GpG dinucleotide. In contrast, a preferred context for hypermutation at the 3' G (or al single G residues) could be defined. In addition to a preference for A residues immediately downstream of hypermutated 3' G residues, C residues were underrepresented in these positions. The observed context fits well with a model whereby G --> A mutation occurs by a combination of dislocation mutagenesis at GpA dinucleotides and direct misincorporation of dTTP at the 5' G of GpG dinucleotides. Furthermore, both runs of six G residues present in the polypurine tracts (PPTs) had escaped hypermutation, despite the fact that 95% of runs of three G residues contained at least one G --> A transition. This finding suggests that genomes with hypermutated PPT motifs had been selected against and provides direct evidence that hypermutation occurs during negative-strand DNA synthesis. (C) 1995 Academic Press, Inc.