APOBEC3G and APOBEC3F rarely co-mutate the same HIV genome.
APOBEC3G and APOBEC3F rarely co-mutate the same HIV genome.
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DOI：
10.1186/1742-4690-9-113
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发表时间：
2012-12-20
期刊：
影响因子：
3.3
通讯作者：
Davenport MP
中科院分区：
文献类型：
--
作者：
Ebrahimi D;Anwar F;Davenport MP
人类免疫蛋白APOBEC 3G和APOBEC 3F（hA 3G和hA 3F）诱导HIV基因组中的破坏性G-至-A变化，称为“超变”。这两种蛋白质在人类细胞中共表达，共定位于mRNA加工体，并可能共包装成HIV病毒体。因此，预计它们也会使HIV基因组发生共突变。在这里，我们研究了hA 3G和hA 3F在大量自然感染患者的全基因组HIV-1序列中的突变足迹，以独特地识别由这两种蛋白中的一种或两种超突变的序列。我们开发了一种基于hA 3G和hA 3F靶向和产物基序的表示的鉴定方法，该方法不需要与亲本/共有序列进行比对。在近100个高度突变的HIV-1序列中，只有一个来自HIV-1异常组的序列显示出两种蛋白质共突变的明显特征。其余序列受hA 3G或hA 3F影响。使用一种新的方法，鉴定的HIV序列hypermutated的hA 3G和hA 3F酶，我们报告了一个非常低的率的全长HIV序列的共突变，并讨论了潜在的机制。
The human immune proteins APOBEC3G and APOBEC3F (hA3G and hA3F) induce destructive G-to-A changes in the HIV genome, referred to as ‘hypermutation’. These two proteins co-express in human cells, co-localize to mRNA processing bodies and might co-package into HIV virions. Therefore they are expected to also co-mutate the HIV genome. Here we investigate the mutational footprints of hA3G and hA3F in a large population of full genome HIV-1 sequences from naturally infected patients to uniquely identify sequences hypermutated by either or both of these proteins. We develop a method of identification based on the representation of hA3G and hA3F target and product motifs that does not require an alignment to a parental/consensus sequence. Out of nearly 100 hypermutated HIV-1 sequences only one sequence from the HIV-1 outlier group showed clear signatures of co-mutation by both proteins. The remaining sequences were affected by either hA3G or hA3F. Using a novel method of identification of HIV sequences hypermutated by the hA3G and hA3F enzymes, we report a very low rate of co-mutation of full-length HIV sequences, and discuss the potential mechanisms underlying this.
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