Sequence determinants of breakpoint location during HIV-1 intersubtype recombination.

Sequence determinants of breakpoint location during HIV-1 intersubtype recombination.
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HIV-1跨型重组期间断点位置的序列决定因素。

DOI:
10.1093/nar/gkl669
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发表时间:
2006
影响因子:
14.9
通讯作者:
Negroni M
Negroni M
中科院分区:
生物学2区
文献类型:
--
作者:
Baird HA;Galetto R;Gao Y;Simon-Loriere E;Abreha M;Archer J;Fan J;Robertson DL;Arts EJ;Negroni M

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逆转录病毒重组是由逆转录过程中病毒中存在的两个基因组RNA拷贝之间的链转换引起的。我们分析了HIV-1亚型A和D毒株之间包膜基因部分的重组。在单个感染循环后,断点聚集在对应于Env恒定部分的区域中。除了一些例外,在多个感染周期后以及在HIV序列数据库中的重组序列中观察到类似的分布。我们将实验数据与计算机模拟进行了比较,计算机模拟使用的程序只允许重组发生时,一个相同的碱基存在于对齐的亲本RNA。实验重组比基于模拟重组的预期更频繁,当在从断裂点的5′边界跨越40 nt的区域中,亲本RNA之间存在不超过两个不一致碱基时。当这些要求没有得到满足时,断裂点沿RNA随机沿着分布,更接近计算机模拟预测的分布。重组的一个显着的偏好,也观察到含有均聚物的延伸区域。这些结果定义,第一次,当地的序列决定因素不同的HIV-1分离株之间的重组。
Retroviral recombination results from strand switching, during reverse transcription, between the two copies of genomic RNA present in the virus. We analysed recombination in part of the envelope gene, between HIV-1 subtype A and D strains. After a single infection cycle, breakpoints clustered in regions corresponding to the constant portions of Env. With some exceptions, a similar distribution was observed after multiple infection cycles, and among recombinant sequences in the HIV Sequence Database. We compared the experimental data with computer simulations made using a program that only allows recombination to occur whenever an identical base is present in the aligned parental RNAs. Experimental recombination was more frequent than expected on the basis of simulated recombination when, in a region spanning 40 nt from the 5′ border of a breakpoint, no more than two discordant bases between the parental RNAs were present. When these requirements were not fulfilled, breakpoints were distributed randomly along the RNA, closer to the distribution predicted by computer simulation. A significant preference for recombination was also observed for regions containing homopolymeric stretches. These results define, for the first time, local sequence determinants for recombination between divergent HIV-1 isolates.
DOI: 10.1074/jbc.m405476200
发表时间: 2004-08-27
影响因子: 4.8
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