Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination.
Analysis of HIV-1 intersubtype recombination breakpoints suggests region with high pairing probability may be a more fundamental factor than sequence similarity affecting HIV-1 recombination.
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DOI：
10.1186/s12985-016-0616-1
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发表时间：
2016-09-21
期刊：
影响因子：
4.8
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Jia L;Li L;Gui T;Liu S;Li H;Han J;Guo W;Liu Y;Li J
随着关于HIV-1的数据越来越多，描述HIV-1基因重组机制细节的更相关的分子模型通常需要升级。目前对复制选择机制的不完整的结构理解以及该领域缺乏阐明的其他几个问题使我们对断点分布与(1)碱基配对概率和(2)亚型间遗传相似性之间的相关性进行了分析，以进一步探索结构机制。从洛斯阿拉莫斯艾滋病病毒数据库中检索来自亚洲、欧洲和非洲的近全长urf序列（一个序列/患者），以及世界范围内具有代表性的crf序列。用jpHMM详细分析了它们的重组模式。然后研究了断点分布与(1)碱基配对概率和(2)亚型间遗传相似性之间的关系。Pearson相关检验显示，所有URF组与CRF组均表现出相同的断点分布模式。此外，Wilcoxon双样本检验表明，在配对概率高的区域，重组存在显著且无法解释的限制。这些区域被发现在不同的生物状态下具有很强的保守性（即强亚型间相似性），遗传相似性被确定为促进重组的一个非常重要的因素。因此，结果揭示了亚型间相似性和断点分布之间的意外差异，遗传相似性分析进一步证实了这一点。我们的分析揭示了天然HIV-1分离株的结果与基于HIV-1的检测载体的结果之间的关键冲突，其中遗传相似性已被证明是促进重组的一个非常关键的因素。这些结果表明，在自然HIV-1感染中，具有高配对概率的区域可能是影响HIV-1重组的更根本因素，而不是序列相似性。我们的发现将有助于进一步了解HIV-1重组机制。本文的在线版本（doi:10.1186/s12985-016-0616-1）包含补充材料，可供授权用户使用。
With increasing data on HIV-1, a more relevant molecular model describing mechanism details of HIV-1 genetic recombination usually requires upgrades. Currently an incomplete structural understanding of the copy choice mechanism along with several other issues in the field that lack elucidation led us to perform an analysis of the correlation between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarity to further explore structural mechanisms. Near full length sequences of URFs from Asia, Europe, and Africa (one sequence/patient), and representative sequences of worldwide CRFs were retrieved from the Los Alamos HIV database. Their recombination patterns were analyzed by jpHMM in detail. Then the relationships between breakpoint distributions and (1) the probability of base pairing, and (2) intersubtype genetic similarities were investigated. Pearson correlation test showed that all URF groups and the CRF group exhibit the same breakpoint distribution pattern. Additionally, the Wilcoxon two-sample test indicated a significant and inexplicable limitation of recombination in regions with high pairing probability. These regions have been found to be strongly conserved across distinct biological states (i.e., strong intersubtype similarity), and genetic similarity has been determined to be a very important factor promoting recombination. Thus, the results revealed an unexpected disagreement between intersubtype similarity and breakpoint distribution, which were further confirmed by genetic similarity analysis. Our analysis reveals a critical conflict between results from natural HIV-1 isolates and those from HIV-1-based assay vectors in which genetic similarity has been shown to be a very critical factor promoting recombination. These results indicate the region with high-pairing probabilities may be a more fundamental factor affecting HIV-1 recombination than sequence similarity in natural HIV-1 infections. Our findings will be relevant in furthering the understanding of HIV-1 recombination mechanisms. The online version of this article (doi:10.1186/s12985-016-0616-1) contains supplementary material, which is available to authorized users.
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影响因子：
56.9
作者：
PELISKA, JA;BENKOVIC, SJ
通讯作者：
BENKOVIC, SJ
影响因子：
4.8
作者：
Galetto, R;Moumen, A;Negroni, M
通讯作者：
Negroni, M
DOI：
10.1016/j.biocel.2004.02.029
发表时间：
2004-09-01
影响因子：
4
作者：
Marchand, B;Götte, M
通讯作者：
Götte, M
DOI：
10.1073/pnas.86.21.8343
发表时间：
1989-11-01
影响因子：
11.1
作者：
PERRINO, FW;PRESTON, BD;LOEB, LA
通讯作者：
LOEB, LA
影响因子：
5.4
作者：
Pfeiffer, JK;Telesnitsky, A
通讯作者：
Telesnitsky, A