Effects of varying sequence similarity on the frequency of repeat deletion during reverse transcription of a human immunodeficiency virus type I vector
Effects of varying sequence similarity on the frequency of repeat deletion during reverse transcription of a human immunodeficiency virus type I vector
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DOI：
10.1128/jvi.76.15.7897-7902.2002
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发表时间：
2002-08-01
影响因子：
5.4
通讯作者：
Telesnitsky, A
中科院分区：
文献类型：
--
作者：
An, WF;Telesnitsky, A
基因重组有助于人类免疫缺陷病毒 1 型 (HIV-1) 的多样性，同源重组比非同源重组更频繁。在本研究中，使用基于 HIV-1 的载体来分析不同程度的序列分歧对重复删除的重组相关特性频率的影响。序列变异的程度类似于区分天然 HIV-1 分离株的程度，是通过同义替换引入基因片段的。然后将该片段的重复拷贝引入测定载体中。通过使用表型筛选，将相同重复的缺失频率与序列不同程度不同的重复的频率进行比较。在 HIV-1 逆转录过程中，差异 5% 的重复序列中观察到的缺失频率是相同重复序列中观察到的删除频率的 65%。当重复相差9%时，删除频率下降至26%，而当重复相差18%时，删除频率约为相同重复值的5%。当检查 27% 或更大的遗传距离时，删除频率降至相同重复值的 0.3% 以下。这些数据表明，遗传变异对 HIV-1 重复删除的抑制作用不如对相应细胞过程的抑制作用大，并且表明，对于差异约 25% 或更多的序列，由序列同源性指导的 HIV-1 重组可能并不比同源性独立重组更频繁。
Genetic recombination contributes to human immunodeficiency virus type 1 (HIV-1) diversity, with homologous recombination being more frequent than nonhomologous recombination. In this study, HIV-1-based vectors were used to assay the effects of various extents of sequence divergence on the frequency of the recombination-related property of repeat deletion. Sequence variation, similar in degree to that which differentiates natural HIV-1 isolates, was introduced by synonymous substitutions into a gene segment. Repeated copies of this segment were then introduced into assay vectors. With the use of a phenotypic screen, the deletion frequency of identical repeats was compared to the frequencies of repeats that differed in sequence by various extents. During HIV-1 reverse transcription, the deletion frequency observed with repeats that differed by 5% was 65% of that observed with identical repeats. The deletion frequency decreased to 26% for repeats that differed by 9%, and when repeats differed by 18%, the deletion frequency was about 5% of the identical repeat value. Deletion frequencies fell to less than 0.3% of identical repeat values when genetic distances of 27% or more were examined. These data argue that genetic variation is not as inhibitory to HIV-1 repeat deletion as it is to the corresponding cellular process and suggest that, for sequences that differ by about 25% or more, HIV-1 recombination directed by sequence homology may be no more frequent than that which is homology independent.