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复杂的正选择压力驱动不同细胞嗜性HIV-1的进化

, PP. 109-120

Keywords: HIV-1细胞嗜性,适应性进化,正选择位点,R5和X4,Gp120,抗原表位

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Abstract:

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.

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