McCutchan F E, Salminen M O, Carr J K, Burke D S
Henry M. Jackson Foundation, Rockville, MD 20850, USA.
AIDS. 1996 Dec;10 Suppl 3:S13-20.
HIV-1 evolves by rapid mutation and by recombination, both processes actively contributing to its genetic diversity. Most of the multiple genetic subtypes and intersubtype recombinations of HIV-1 that comprise the global pandemic have not been characterized by full genome sequencing.
DNA from primary virus cultures on donor peripheral blood mononuclear cells was used as template for long polymerase chain reaction amplification, molecular cloning, and automated sequencing of virtually full-length HIV-1 genomes from subtypes A, C, E, G and A/D recombinant forms. Standard phylogenetic analysis methods were employed, and some were modified for the detection and mapping of recombinant breakpoints.
Subtypes A, B, C and D are largely, if not entirely, distinguishable throughout the genome and show no clear evidence of intersubtype recombination. In contrast, all available sequences of subtypes E and G are recombinant with subtype A. Full-length sequences of subtypes F, H, I and J are still unavailable. Subtype E and G, and some A/D recombinant HIV, have retained the cytoplasmic domain of gp41 from subtype A. Some recombinants possess the matrix and core of one subtype and the outer envelope of another, resembling pseudotypes. Certain pairs of subtypes may have recombined more often than others.
Recombinant HIV-1 have already established a global reservoir and are largely responsible for the rapidly expanding subtype E epidemic in Southeast Asia. Recombination may have played a key role in the evolution of HIV-1 and the geographic intermixing of subtypes, which is increasing, may foster the emergence of a even greater variety of recombinant strains.
HIV-1通过快速突变和重组进行演变，这两个过程都积极地促进了其基因多样性。构成全球大流行的HIV-1的多种基因亚型和亚型间重组中的大多数尚未通过全基因组测序进行表征。
将来自供体外周血单个核细胞的原代病毒培养物中的DNA用作模板，进行长聚合酶链反应扩增、分子克隆以及对来自A、C、E、G亚型和A/D重组形式的几乎全长HIV-1基因组进行自动测序。采用标准的系统发育分析方法，并对其中一些方法进行了修改以检测和定位重组断点。
A、B、C和D亚型在整个基因组中在很大程度上（如果不是完全）是可区分的，并且没有明显的亚型间重组证据。相比之下，E和G亚型的所有可用序列均与A亚型重组。F、H、I和J亚型的全长序列仍然不可用。E和G亚型以及一些A/D重组HIV保留了A亚型gp41的胞质结构域。一些重组体具有一种亚型的基质和核心以及另一种亚型的外膜，类似于假型。某些亚型对之间的重组可能比其他亚型对更频繁。
重组HIV-1已经建立了一个全球储存库，并且在很大程度上导致了东南亚地区E亚型疫情的迅速蔓延。重组可能在HIV-1的进化以及亚型的地理混合中发挥了关键作用，而这种混合正在增加，可能会促进更多种类重组毒株的出现。
