HIV-1 B’亚型感染者Nef蛋白CTL表位变异与病毒载量的相关性  

Association between CTL epitope variations of Nef protein and viral loads in HIV-1 B' infectors

作　　者：胡园园[1] 陈燕丽[1] 张岱[1] 邹森[1] 侯佳莉 任莉[1] 郝彦玲[1] 

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,传染病预防控制国家重点实验室,北京102206

出　　处：《中国热带医学》2016年第11期1070-1073,共4页China Tropical Medicine

基　　金：国家自然科学基金(No.81172809)

摘　　要：目的探讨HIV-1 B’亚型毒株感染者Nef蛋白细胞毒性淋巴细胞(cytotoxic T lymphocyte,CTL)表位变异及其与病毒载量的相关性。方法从137例HIV-1 B’亚型毒株感染者的血浆样本中提取病毒RNA,经逆转录及巢式PCR扩增获得Nef基因并测序,将获得的Nef基因序列翻译为蛋白序列,然后与HIV免疫学数据库中经过实验证实的CTL表位进行比对,分析Nef蛋白CTL表位变异与感染者病毒载量的关系。结果与HIV免疫学数据库中CTL表位的比较发现,本研究137例HIV-1 B’亚型毒株感染者病毒Nef蛋白大部分CTL表位相对保守,只有5个表位的变异频率超过10%,CTL表位旁序列的变异程度较锚着位点变异大,表位旁上下游第一位氨基酸的突变频率较高,表位氨基酸总变异频率、锚着位点和表位旁序列的氨基酸变异频率与病毒载量呈正相关,非锚着位点氨基酸的变异与病毒载量无相关性。结论 HIV-1 B’亚型毒株感染者Nef蛋白大部分CTL表位较保守,CTL表位旁序列变异程度较锚着位点大,表位旁上下游第一位氨基酸的突变频率较高,推测表位旁序列氨基酸的变异可能是Nef蛋白CTL逃逸突变的主要方式,Nef蛋白CTL表位变异与病毒适应性损伤的关系还需进一步研究。Objective We explored the potential relationship between cytotoxic T lymphocyte（CTL） epitope variations ofNef protein and viral loads in HIV-1 B＇ infectors. Methods Viral RNAs were isolated from 137 plasm samples of HIV-1 B＇infectors and c DNAs were synthesized by reverse transcription. Nef genes were amplified by RT- and nested-PCR, and PCRproducts were sequenced directly,and then translated into protein sequence. Nef protein sequences were compared with theexperiment-validated CTL epitopes in HIV immunology database. The CTL epitope variation of Nef protein and its influence onthe viral load of the infected person were analyzed. Results Compared with the CTL epitopes in the HIV immunologydatabase, there were a few of variation in most CTL epitopes of the Nef protein in 137 HIV-1 B＇ infected individuals. Therewere only 5 epitopes with a mutation frequency of more than 10%. The variation of flank region was more frequently observedthan the anchor site, there was a positive correlation between the viral load and the frequency of variation in total epitopes,anchor site and flank region. However, we didn＇t observed a positive correlation between the viral load and the frequency ofvariation in non-anchor site. Conclusion There are relatively conservative in most CTL epitopes of Nef protein,the variationof flank region was more frequently than the anchor site in CTL epitope, the frequency of first amino acid mutation to upstreamand downstream of flank region is higher,the variation of amino acid sequence in flank region may be the main way of escapemutation of Nef protein.The relationship of the variation in CTL epitopes and the damage of viral fitness needs further study。

关 键 词：HIV-1 NEF蛋白 CTL表位 病毒载量 

分 类 号：R512.91[医药卫生—内科学]