Pervasive and non-random recombination in near full-length HIV genomes from Uganda
Pervasive and non-random recombination in near full-length HIV genomes from Uganda
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DOI：
10.1093/ve/veaa004
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发表时间：
2020-01-01
期刊：
影响因子：
5.3
通讯作者：
Brown, Andrew J. Leigh
中科院分区：
文献类型：
--
作者：
Grant, Heather E.;Hodcroft, Emma B.;Brown, Andrew J. Leigh
变异是艾滋病毒进化的一个重要特征，在主要的多样性分支（亚型）内部和之间发生。乌干达的流行病主要由两种亚型组成，A1和D，这两种亚型已经共同传播了50年，经常在双重感染的患者中重组。在这里，我们调查的频率重组在这个人口和断裂点的位置沿着基因组。作为PANGEA-HIV联盟的一部分，从MRC/UVRI & LSHTM研究单位在乌干达收集的1 857个样本中获得了1 472个5 kb以上的共有基因组序列，其中465个（31.6%）接近全长序列（>8 kb）。使用子类型化工具SCUEAL，我们发现在接近全长的数据集中，233（50.1%）基因组仅包含一种亚型，30.8%的A1（n = 143），17.6%的D（n = 82）和1.7%的C（n = 8），49.9%（n = 232）的标本含有一种以上亚型（包括A1/D型164例，A1/C型13例，C/D型9例，A1/C/D型13例，复合型33例）。重组A1/D基因组的K-均值聚类揭示了一段包膜（C2 gp 120-TMgp 41）通常是完整遗传的，而广义线性模型被用来证明与辅助基因区域相比，gag-pol和包膜C2-TM区域中的断点显著较少。尽管在许多重组体中有类似的重组模式，但没有发现明确支持的循环重组形式（CRF），断点传输的证据有限，绝大多数（153/164; 93%）的A1/D重组体似乎是独特的重组形式。因此，重组是普遍的，在断点位置有明显的偏差，但CRF不是一个重要的特征，一个复杂的，多样的流行病的特征。
Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (n = 9); A1/C/D (n = 13), and 33 complex types). K-means clustering of the recombinant A1/D genomes revealed a section of envelope (C2gp120-TMgp41) is often inherited intact, whilst a generalized linear model was used to demonstrate significantly fewer breakpoints in the gag-pol and envelope C2-TM regions compared with accessory gene regions. Despite similar recombination patterns in many recombinants, no clearly supported circulating recombinant form (CRF) was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93 per cent) of the A1/D recombinants appear to be unique recombinant forms. Thus, recombination is pervasive with clear biases in breakpoint location, but CRFs are not a significant feature, characteristic of a complex, and diverse epidemic.