Identification of an HIV-1 BG Intersubtype Recombinant Form (CRF73_BG), Partially Related to CRF14_BG, Which Is Circulating in Portugal and Spain

HIV-1 exhibits a characteristically high genetic diversity, with the M group, responsible for the pandemic, being classified into nine subtypes, 72 circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs). Here we characterize the near full-length genome sequence of an HIV-1 BG intersubtype recombinant virus (X3208) collected in Galicia (Northwest Spain) which exhibits a mosaic structure coincident with that of a previously characterized BG recombinant virus (9601_01), collected in Germany and epidemiologically linked to Portugal, and different from currently defined CRFs. Similar recombination patterns were found in partial genome sequences from three other BG recombinant viruses, one newly derived, from a virus collected in Spain, and two retrieved from databases, collected in France and Portugal, respectively. Breakpoint coincidence and clustering in phylogenetic trees of these epidemiologically-unlinked viruses allow to define a new HIV-1 CRF (CRF73_BG). CRF73_BG shares one breakpoint in the envelope with CRF14_BG, which circulates in Portugal and Spain, and groups with it in a subtype B envelope fragment, but the greatest part of its genome does not appear to derive from CRF14_BG, although both CRFs share as parental strain the subtype G variant circulating in the Iberian Peninsula. Phylogenetic clustering of partial pol and env segments from viruses collected in Portugal and Spain with X3208 and 9691_01 indicates that CRF73_BG is circulating in both countries, with proportions of around 2–3% Portuguese database HIV-1 isolates clustering with CRF73_BG. The fact that an HIV-1 recombinant virus characterized ten years ago as a URF has been shown to represent a CRF suggests that the number of HIV-1 CRFs may be much greater than currently known.人类免疫缺陷病毒1型（HIV-1）具有显著的高遗传多样性，引发全球大流行的M组可分为9个亚型、72种流行重组型（circulating recombinant forms，CRFs）以及大量独特重组型（unique recombinant forms，URFs）。本研究对一株采集自西班牙西北部加利西亚地区的HIV-1 BG亚型间重组病毒（X3208）的近全长基因组序列进行了表征，该病毒的嵌合基因组结构与此前已报道的德国分离株BG重组病毒9601_01完全一致；9601_01株与葡萄牙存在流行病学关联，且其基因型不同于当前已定义的所有流行重组型。另有三株BG重组病毒的部分基因组序列也呈现出相同的重组模式：其中一株为新获得的西班牙分离株，另外两株分别为从数据库中调取的法国和葡萄牙分离株。上述无流行病学关联的病毒株的重组断点一致性及其在系统发育树中的聚类特征，共同支持定义一种新型HIV-1流行重组型——CRF73_BG。CRF73_BG在包膜（env）蛋白编码区存在一处与CRF14_BG一致的重组断点；CRF14_BG在葡萄牙与西班牙地区流行，其包膜蛋白B亚型片段与CRF73_BG聚类，但CRF73_BG的大部分基因组序列并非源自CRF14_BG——尽管两类流行重组型的亲本毒株均为在伊比利亚半岛流行的G亚型变异株。对葡萄牙和西班牙分离株的聚合酶（pol）及包膜（env）部分基因片段进行的系统发育聚类分析显示，X3208与9691_01株均与上述两国的分离株聚类，表明CRF73_BG在两国均有流行；在葡萄牙数据库的HIV-1分离株中，约2%~3%的序列与CRF73_BG聚类。一株十年前被鉴定为独特重组型的HIV-1重组病毒，后续被证实属于某一流行重组型，这一现象提示，当前已知的HIV-1流行重组型数量远低于实际存在的规模。