CAJ | 학술논문

目的了解我国B'亚型HIV gag基因随时间进化的特征及阳性选择位点与宿主HLA限制性CTL应答的关系.方法从HIV序列数据库下载我国B’亚型HIV-1 gag序列,计算不同年代病毒多样性及基因离散率,应用Hyphy软件分析Gag蛋白阳性选择位点及其与HLA限制性CTL应答的关系.结果本研究共获得来自河南、湖北、辽宁及云南地区的122条B '亚型gag序列,按采样时间分为4组:＜2001、2001-2003、2004-2006及2007-2010年,病毒多样性及离散率均随时间逐渐增加(r1=0.497,P1＜0.001；r2 =0.593,P2＜0.001)；Gag蛋白34个阳性选择位点中97.1％位于已明确的47个HLA限制性CTL表位内,HLA-A、B、C限制表位分别占43.1％、49.0％及7.9％.结论我国B’亚型gag基因多样性及离散率随着流行时间延长逐渐增加,B '亚型毒株正逐渐适应我国人群常见的HLA限制性CTL应答,提示该毒株疫苗研发时需要注意避免选用相关CTL表位为免疫原.
목적 료해아국B'아형HIV gag기인수시간진화적특정급양성선택위점여숙주HLA한제성CTL응답적관계.방법 종HIV서렬수거고하재아국B’아형HIV-1 gag서렬,계산불동년대병독다양성급기인리산솔,응용Hyphy연건분석Gag단백양성선택위점급기여HLA한제성CTL응답적관계.결과 본연구공획득래자하남、호북、료녕급운남지구적122조B '아형gag서렬,안채양시간분위4조:＜2001、2001-2003、2004-2006급2007-2010년,병독다양성급리산솔균수시간축점증가(r1=0.497,P1＜0.001；r2 =0.593,P2＜0.001)；Gag단백34개양성선택위점중97.1％위우이명학적47개HLA한제성CTL표위내,HLA-A、B、C한제표위분별점43.1％、49.0％급7.9％.결론 아국B’아형gag기인다양성급리산솔수착류행시간연장축점증가,B '아형독주정축점괄응아국인군상견적HLA한제성CTL응답,제시해독주역묘연발시수요주의피면선용상관CTL표위위면역원.
Objective To identify the genetic variation of Gag gene in HIV-1 B' subtype infected Chinese people and to evaluate the association between the positive selection sites and HLA restricted CTL response.Methods We downloaded all HIV-1 B' subtype gag gene sampled from China from the LANL HIV database.The sequences were grouped by years of collection and the mean intra-subtype diversity and divergence were examined by MEGA 5.0 software.The sites under positive selection were estimated by using Hyphy software.Then analyzed the association between positively selected sites and HLA restricted CTL epitopes.Results A set of 122 B' subtype HIV-1 gag sequences were collected from Henan,Hubei,Liaoning and Yunnan provinces,grouped by sampling year as ＜ 2001,2001-2003,2004-2006 and 2007-2010.The mean intra-subtype diversity and divergence increased over time (r1 =0.497,P1 ＜ 0.001 ;r2 =0.593,P2 ＜ 0.001).This analysis revealed 34 positively selected sites and 97.1％ of these sites were located within 47 known CTL epitopes.The most frequent HLA was HLA-A * 02(21.6％) followed by A *11 (9.8％),B * 35 (9.8％) and B * 57 (5.9％).The percentages of HLA-A/B/C limited CTL epitopes were 43.1％,49.0％ and 7.9％,respectively.Conclusion The mean intra-subtype diversity and divergence of B' subtype gag sequences increased over time.B' subtype HIV-1 virus has accumulated adaptations to HLA restricted CTL responses in HIV-1 infected Chinese.