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对HIV-1细胞嗜性的研究是理解HIV-1传播和发病机制的关键.通过对HIV-1B和C亚型的R5和X4型病毒的全基因组进行适应性进化分析,发现R5和X4病毒经历了不同的进化方式,并且不同的HIV-1基因受到不同的正选择压力,意味着复杂的自然选择压力驱动HIV-1的进化.分析HIV-1Gp120超变区上的正选择位点,发现相对于其他超变区,更多的正选择位点发生在B亚型X4病毒的V3区,B亚型R5病毒的V2区以及C亚型X4病毒的V1和V4区域.因为这些区域通常影响和决定HIV-1的细胞嗜性,更多的正选择发生在这些特定的超变区意味着作用于Gp120上的选择压力与Gp120的受体识别和结合功能有关.值得注意的是,无论是B和C亚型还是R5和X4型病毒,显著更多的正选择位点发生在Gp120的C3区域(33.3%～55.6%,P<0.05),意味着C3区对HIV-1的生存和适应比先前认识的更为重要.另外,在R5和X4病毒的env基因中,约有一半的正选择位点是相同的,尤其是Gp41上的第96,113和281位正选择位点均出现在所分析的4种病毒类型中.这些共同的正选择位点不仅意味着对病毒生存和适应的重要性,也意味着R5和X4存在交叉免疫源性位点的可能性,这对于AIDS疫苗的发展具有重要意义.
The study of HIV-1 cell tropism is the key to understanding the transmission and pathogenesis of HIV-1. By analyzing the whole genome of R5 and X4 viruses of HIV-1B and C subtypes adaptively, it was found that R5 and X4 viruses Undergoing different evolutionary modalities, and different HIV-1 genes being subjected to different positive selection pressures, implying that complex natural selection pressures drive the evolution of HIV-1.Analysis of positive selection sites on the HIV-1 Gp120 hypervariable region revealed that More of the positive selection sites occur in the V3 region of the B subtype X4 virus, in the V2 region of the B subtype R5 virus and in the V1 and V4 regions of the C subtype X4 virus relative to the other hypervariable regions, since these regions generally affect And determining the cellular tropism of HIV-1, more positive selection occurs in these particular hypervariable regions, implying that the selection pressure acting on Gp120 is related to the receptor recognition and binding function of Gp120 It is noteworthy that both the B and C subtypes were also the R5 and X4 viruses, with significantly more positive selection sites in the C3 region of Gp120 (33.3% -55.6%, P <0.05), implying C3 survival and adaptation to HIV-1 More important than previously recognized.In addition, in the R5 and X4 viruses env gene, about half of the positive selection sites The same, and in particular, the 96, 113 and 281 positive selection sites on Gp41 all appeared in the 4 virus types analyzed.These common positive selection sites not only imply the importance of surviving and adapting to the virus The possibility of cross-immunogenicity of R5 and X4 is important for the development of the AIDS vaccine.