亚洲主要流行HIV-1 Gp120及其5个高变区多态性分析

Polymorphism characteristic of Asia HIV-1 Gp120 and five hypervariable regions

HIV-1 Gp120及其5个高变区的多态性是HIV-1能够逃逸宿主免疫反应和耐药性的主要原因。下载了现有数据库中记载的包括B'、C、CRF01_AE、CRF07_BC和CRF08_BC 5种亚洲主要流行亚型和重组型的所有Gp120及其5个高变区序列,分析了HIV-1 Gp120及其5个高变区序列的长度多态性,糖基化位点数以及序列特征。结果显示,绝大部分的HIV-1 Gp120序列长度为496～515个氨基酸之间,这提示Gp120长度为496～515个氨基酸的HIV-1毒株可能是疫苗研究的理想毒株。比较5个高变区,V3区表现出了最低的长度多态性,几乎没有糖基化位点,表明受到较强的功能限制。不同亚型和重组型的V3区一致序列比较发现,所有的HIV-1亚型均表现为R5型。这提示阻断HIV-1病毒结合CCR5受体是治疗艾滋病的有效途径,R5型毒株可以作为艾滋病疫苗研究的理想毒株。另外,V1和V4区展现了很高的长度多态性,糖基化位点也较多;而V2和V5区的长度多态性和糖基化位点都较低。这些结果表明降低这4个高变区的多态性和糖基化位点数目可能解决HIV-1病毒对疫苗的逃逸,从而研究出真正有效的疫苗。

Polymorphism of HIV-1 Gpl20 and five hypervariable regions have large contributions to HIV-1 escape from the immune attack and/or drug selection. In this study, the length polymorphism, potential number of N-linked glycosylation sites （PNGS） and sequence characteristic of nearly all available Asia Gpl20 from HIV-1 subtypes B＇, C, CRF01_AE, CRF07_BC and CRF08_BC were analyzed. Majority of HIV-1 Gpl20 have 496-515 amino acids, suggesting that HIV-I Gpl20 with 496 -515 amino acid length might be a good candidate protein for vaccine development. Among five hypervariable regions, the V3 regions had the lowest levels of length polymorphism and heterogeneity and PNGS, implying a strong function constraint. The consensus V3 loop sequences of all subtypes ex- hibited R5 tropism, possibly implying that majority of HIV-1 strains are R5 strains. This suggested that CCR5 antagonists may be ex- tremely efficient for AIDS treatment and R5 strains should be used as candidates for AIDS vaccine development. Furthermore, V1 and V4 regions had high levels of length polymorphism and heterogeneity and PNGS, and V2 and V5 exhibited moderate levels of these pa- rameters. These results suggested that new strategies to reduce the polymorphism, heterogeneity and PNGS of the 4 hypervariable regions should be developed to effectively elicit immune response in AIDS vaccine development.