我国HIV-1主要流行株外膜蛋白(env)基因V3～V4区变异及其与生物学特性的关系  

The potential relationship between variation in the env V3-V4 region of HIV-1 predominant strains in China and virus biological feature

作　　者：邢辉[1] 梁浩[2] 洪坤学[1] 魏民[1] 赵全壁[1] 冯毅[1] 陈建平[1] 全宇[1] 滕涛[1] 邵一鸣 

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心,北京100050 [2]广西医科大学公共卫生学院

出　　处：《中华微生物学和免疫学杂志》2005年第3期185-189,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家杰出青年资金项目 ( 3992 5 0 30 ) ;国家"十五"科技攻关项目 ( 2 0 0 1BA70 5B0 2 )

摘　　要：目的　研究我国HIV 1主要流行毒株亚型的envV3～V4区变异与生物学特性的关系。方法　应用nested PCR对 1 57份获自我国 1 2个省份的HIV 1毒株env区序列进行扩增 ,并使用ABI 377型测序仪测序 ,然后应用BLAST、GCG和MEGA等生物学软件或程序对env基因V3～V4区序列进行分析。结果　B′亚型毒株V3顶端四肽存在着 4种类型 :GPGR ( 54% )、GPGQ ( 2 8% )、GPGK( 1 6 % )和GPGA( 2 % ) ,B′/C重组毒株全部为GPGQ( 1 0 0 % ) ,CRF0 1 AE重组毒株呈现GPGQ( 95% )和GPGR( 5% )两种类型 ;B′/C和CRF0 1 AE重组毒株V3～V4区及其临近区域N 糖基化位点比B′亚型毒株N 糖基化位点保守。而B′亚型毒株V3环的净电荷分别显著高于B′/C和CRF0 1 AE毒株 (P <0 .0 1 ) ;根据V3环关键氨基酸推测辅助受体使用情况的结果显示 :B′亚型毒株有 9.2 6 %可能使用CCR5,7.4 1 %可能使用CXCR4 ,其余 83.33%不能对辅助受体的使用作出预测。所有B′/C重组毒株被预测可能使用CCR5。CRF0 1 AE重组毒株有 90 .4 8%被预测可能使用CCR5,没有被预测为使用CXCR4的序列 ,9.52 %不能作出预测。结论　B′亚型毒株大部分可能为NSI型 ,少部分可能为SI型 ,而B′/C和CRF0 1 AE重组毒株绝大部分为NSI型。我国主要流行株的V3～V4区尤其是V3环的氨基酸?Objective To characterize the amino acid sequence variations in the V3 V4 region of the env gene from human immunodeficiency virus type 1 (HIV 1) predominant circulating strains in China and to elucidate the potential relationship between these variations and biological features. Methods Fragments of the HIV 1 env gene were amplified by nested PCR from the peripheral blood of HIV 1 infected individuals from 12 provinces in China. Then, the PCR products were directly sequenced by using ABI 377 DNA SEQUENCER. The sequences covering the env V3 V4 region of the strains were analyzed by BLAST, GCG, and MEGA. Results The subtype B′ strains had four types of V3 loop central motif GPGR(54%), GPGQ(28%), GPGK(16%), and GPGA(2%). The B′/C strains showed only one type GPGQ (100%) while the CRF01 AE strains had two types GPGQ(95%) and GPGR(5%). The N linked glycosylation sites in the V3 V4 and flanking regions of the B′/C and CRF01 AE strains were relatively conserved as compared to those of the subtype B′ strains. In contrast, the subtype B′ strains had significantly higher mean V3 loop net charge than B′/C and CRF01 AE strains ( P <0.01). Predictions for the potential use of co receptors on the basis of the critical amino acids within V3 loop disclosed that 9.26% of the subtype B′ strains were predicted to be CCR5 using (CCR5 +), 7.41% were predicted to be using CXCR4, but the co receptor usage of the vast majority (83.33%) could not be predicted. All of the B′/C strains (100%) were shown to use CCR5 + while the majority of the CRF01 AE strains (90.48%) were predicted to be CCR5 +, none displayed changes that would be predicted for using CXCR4 +, and 9.52% could not be predicted. Conclusion Based on the analysis of amino acid sequences, this study predicts that the majority of subtype B′ strains currently circulating in China are likely to be non syncytium inducing (NSI), while a small proportion are syncytium inducing (SI). The genetic variations in the env V3

关 键 词：生物学特性 流行株 外膜蛋白 基因 NESTED-PCR N-糖基化位点 HIV-1毒株 亚型毒株 CXCR4 可能使用 CCR5 辅助受体 氨基酸变异 enu V3环 流行毒株 方法应用 功能限制 重组 预测 序列 GCG I型 测序 NS 

分 类 号：R346[医药卫生—基础医学]