Grant Heather E, Hodcroft Emma B, Ssemwanga Deogratius, Kitayimbwa John M, Yebra Gonzalo, Esquivel Gomez Luis Roger, Frampton Dan, Gall Astrid, Kellam Paul, de Oliveira Tulio, Bbosa Nicholas, Nsubuga Rebecca N, Kibengo Freddie, Kwan Tsz Ho, Lycett Samantha, Kao Rowland, Robertson David L, Ratmann Oliver, Fraser Christophe, Pillay Deenan, Kaleebu Pontiano, Leigh Brown Andrew J
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK.
Biozentrum, University of Basel, Basel, Switzerland.
Virus Evol. 2020 Feb 11;6(1):veaa004. doi: 10.1093/ve/veaa004. eCollection 2020 Jan.
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 ( = 143), 17.6 per cent D ( = 82), and 1.7 per cent C ( = 8), while 49.9 per cent ( = 232) contained more than one subtype (including A1/D ( = 164), A1/C ( = 13), C/D ( = 9); A1/C/D ( = 13), and 33 complex types). -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.
重组是HIV进化的一个重要特征，在多样性的主要分支（亚型）内部和之间都会发生。乌干达的疫情主要由两种亚型A1和D组成，它们已经共同传播了50年，在双重感染的患者中经常发生重组。在这里，我们调查了该人群中重组体的频率以及基因组上断点的位置。作为泛非艾滋病病毒联盟的一部分，从乌干达MRC/UVRI和伦敦卫生与热带医学院研究单位收集的1857个样本中获得了1472个长度超过5kb的共有基因组序列，其中465个（31.6%）是近全长序列（>8kb）。使用亚型分型工具SCUEAL，我们发现在近全长数据集中，233个（50.1%）基因组仅包含一种亚型，30.8%为A1（=143），17.6%为D（=82），1.7%为C（=8），而49.9%（=232）包含不止一种亚型（包括A1/D（=164）、A1/C（=13）、C/D（=9）；A1/C/D（=13）和33种复杂类型）。对重组A1/D基因组的均值聚类显示，包膜的一部分（C2gp120-TMgp41）通常完整遗传，而广义线性模型用于证明与辅助基因区域相比，gag-pol和包膜C2-TM区域的断点明显更少。尽管许多重组体具有相似的重组模式，但未发现明显支持的循环重组形式（CRF），断点传播的证据有限，并且绝大多数（153/164；93%）的A1/D重组体似乎是独特的重组形式。因此，重组普遍存在，断点位置存在明显偏差，但CRF不是一个显著特征，这是一个复杂多样的疫情的特点。
