我国HIV-1 B′亚型毒株gag基因变异特征研究  

Analysis of gag P17/P24 gene characteristics of HIV-1 subtype B' viruses prevalent in China

作　　者：关琪[1] 邢辉[2] 黄海龙[2] 魏民[2] 洪坤学[2] 马鹏飞[2] 司雪峰[2] 陈健平[2] 梁浩[2] 张卓然[3] 邵一鸣 

机构地区：[1]沈阳医学院奉天医院检验科 [2]中国疾病预防控制中心性病艾滋病预防与控制中心病毒免疫室,北京100050 [3]大连医科大学微生物学教研室

出　　处：《中华微生物学和免疫学杂志》2007年第10期923-927,共5页Chinese Journal of Microbiology and Immunology

基　　金：卫生部艾滋病防治应用研究项目(WA2003-01);国家杰出青年资金资助项目(39925030)

摘　　要：目的研究我国人免疫缺陷病毒1型(HIV-1)B’亚型主要流行株在宿主免疫压力下的基因变异及抗原表位的变化特征,探讨选择压力、基因离散率和抗原表位变化之间的关系。方法从确诊的HIV-1感染并的全血样本中提取基因组DNA,经套式聚合酶链反应(PCR)扩增后,将扩增产物进行纯化和测序。然后将所得序列进行系统进化树和氨基酸变异分析,使用GCG软件包的Distance程序对P17和P24两个区段计算基因距离,用Diverge程序计算同义替换(Ks)和非同义替换(Ka)及二者之间的比值,并对我国人群中较常见的HLA型别限制的CTL表位的突变情况进行分析。结果HIV-1 B’亚型毒株的P17区段的Ks/Ka值<1,而P24区段的Ks/Ka值>1;P24部分的基因离散率低于P17部分;P17区段抗原表位的保守率为34.94%,而P24区段抗原表位的保守率为67.38%;从基因离散率、所受的选择压力及抗原表位的突变率3个方面来看,HIV-1的P17区段均明显大于P24区段。结论HIV-1 B’亚型毒株的P17区段的抗原表位变化较大,而P24区段的抗原表位相对较为保守。提示P24区段的CTL表位更适合于表位疫苗的研制。Objective To study the characteristics of gene variation and changes of antigen epitopes of HIV-1 subtype B＇ viruses prevalent in China under the host immune pressures, and to explore the relationship among the immune pressures, gene distance and variations of antigen epitopes. Methods Genomic DNA was extracted from the pheripheral blood samples collected from HIV-1 positive anti-retrovirus therapy naive patient. Nested-PCR was carried out and PCR products were purified and used directly for sequencing. The analysis of the gene-based phylogenetic nee and variation of amino acid were carried out. The gene distances of both P17 and P24 regions were calculated by Distance program with GCG software. The accumulation of synonymous （Ks） and antonymous （Ka） substitutions as well as Ks/Ka ratios were calculated using Diverge. The variation analysis of CIL antigen epitopes restricted by main HLA specificities in China was performed. Results Ks/Ka ratio is statistically below 1.0 in P17 region, at the same time, the Ks/Ka ratio is lower 1.0 in the P24 region. Gene homology in P24 is higher than that of P17 region. Conservation of P17 epitopes are 34.94% and 67.38% in P24 region. This trend is consistent with the changes of gene distances and immune pressures of Chinese subtype B＇ strains. The data show that P17 region seems to face more immune pressures, and display more genetic diversity and variation of epitopes than P24 region. Conclusion More diversity of antigen epitopes in gag P17 region than that in P24 was observed in HIV-1 subtype B＇ viruses prevalent in China.

关 键 词：HIV-1 序列分析 基因型 变异(遗传学) 抗原 表位 

分 类 号：R373[医药卫生—病原生物学]