HIV-1感染长期不进展者中env基因准种序列和中和活性相关性  

Correlation between env quasispecies sequence and neutralization activity in HIV-1 infected long-term non-progressors

作　　者：陈敏[1] 戴洁[1] 傅莉莉 陈会超[1] 董莉娟[1] 金晓媚[1] 杨敏 史宣玲 马艳玲[1] CHEN Min;DAI Jie;FU Lili;CHEN Huichao;DONG Lijuan;JIN Xiaomei;YANG Min;SHI Xuanling;MA Yanling(Institute for AIDS/STDs Control and Prevention,Yunnan Provincial Center for Disease Control and Prevention,Kunming 650022,Yunnan,China;Comprehensive AIDS Research Center,School of Medicine,Tsinghua University,Beijing 100084)

机构地区：[1]云南省疾病预防控制中心性病艾滋病防制所,昆明650022 [2]清华大学医学院艾滋病综合研究中心,北京100084

出　　处：《中国艾滋病性病》2020年第10期1041-1044,共4页Chinese Journal of Aids & STD

基　　金：国家自然科学基金项目(81560327);云南省医疗卫生单位内设研究机构科研项目(2016NS136)。

摘　　要：目的分析1型艾滋病病毒(HIV-1)感染长期不进展者中病毒准种序列的特征和中和活性的相关性。方法选择云南省报告8年以上、未接受抗病毒治疗且CD4+T淋巴细胞计数>500个/μL的HIV-1感染者15例,通过假病毒中和实验对样品的中和活性进行分析,对三种不同基因型假病毒中和抑制率均>50%认为具有交叉中和活性,对env基因片段进行高通量测序和序列分析。结果5个样品具有交叉中和活性,另外10个样品无交叉中和活性。构成比>1%的准种在有交叉中和活性样品中的种类(15.80±0.86)多于无交叉中和活性样品中的种类(10.20±1.32)。构成比>1%的准种在有交叉中和活性样品中的合计构成比(0.4264±0.0401)小于无交叉中和活性样品中的合计构成比(0.6434±0.0227)。首位准种在有交叉中和活性样品中的比例(0.0823±0.0119)小于无交叉中和活性样品中的比例(0.2891±0.0307)。准种序列间在有交叉中和活性样品中的平均基因距离(0.0401±0.0023)大于无交叉中和活性样品中的平均基因距离(0.0173±0.0026)。结论HIV-1感染长期不进展者中准种序列的构成与中和活性有相关性,有交叉中和抗体活性的样品中优势准种在弱化,劣势准种得到增强,不同准种的频率差异减小,准种间的基因距离增加。Objective To analyze the correlation between the characteristics of viral quasispecies and neutralizing activity in HIV-1 infected long-term non-progressors(LTNPs).Methods A total of 15 HIV-1 infected cases diagnosed over 8 years,not receiving antiretroviral therapy and with CD4+T lymphocytes>500 cells/μL were collected in Yunnan.The neutralizing activities were analyzed with pseudovirus neutralization testing,and cross-neutralizing activity was confirmed when the neutralization inhibition rates for all three pseudoviruses with different genotypes were larger than 50%.The quasispecies of env were obtained with high-throughput sequencing and were further analyzed.Results A total of 5 samples had cross-neutralizing activity,and the other 10 had no cross-neutralizing activity.The number of quasispecies with a constituent ratio of more than 1%in the samples with cross-neutralizing activity(Mean±SEM:15.80±0.86)was more than that in the sample without cross-neutralizing activity(Mean±SEM:10.20±1.32).The total constituent ratio of all quasispecies with a constituent ratio of more than 1%in the samples with cross-neutralizing activity(Mean±SEM:0.4264±0.0401)was less than that in the sample without cross-neutralizing activity(Mean±SEM:0.6434±0.0227).The constituent ratio of the leading quasispecies in the samples with cross-neutralizing activity(Mean±SEM:0.0823±0.0119)was less than that in the sample without cross-neutralizing activity(Mean±SEM:0.2891±0.0307).The average genetic distance of quasispecies in the samples with cross-neutralizing activity(Mean±SEM:0.0401±0.0023)was less than that in the sample without cross-neutralizing activity(Mean±SEM:0.0173±0.0026).Conclusion The composition of quasispecies is correlated with the neutralization activity in LTNPs.The dominant quasispecies are weakened,and the inferior quasispecies strengthened.The frequency difference of different quasispecies decreases and the genetic distances among quasispecies increases.

关 键 词：1型艾滋病病毒 长期不进展者 中和活性抗体 准种 

分 类 号：R512.91[医药卫生—内科学]