Dynamics of HIV-1 quasispecies diversity of participants on long-term antiretroviral therapy based on intrahost single-nucleotide variations
Dynamics of HIV-1 quasispecies diversity of participants on long-term antiretroviral therapy based on intrahost single-nucleotide variations
复制标题
基于宿主内单核苷酸变异的长期抗逆转录病毒治疗参与者的 HIV-1 准种多样性动态
DOI：
10.1016/j.ijid.2021.01.015
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发表时间：
2021
影响因子：
8.4
通讯作者：
Liying Ma
中科院分区：
文献类型：
--
作者：
Yuanyuan Zhang;Qianqian Yin;Ming Ni;Tingting Liu;Chen Wang;Chuan Song;Lingjie Liao;Hui Xing;Shibo Jiang;Yiming Shao;Chen Chen;Liying Ma
目的人类免疫缺陷病毒（HIV）准种多样性是消除HIV的一大障碍。本研究的目的是调查宿主内HIV准种多样性和进化模式的基础上的抗逆转录病毒疗法（ART）的病毒发病机制。MethodsForty 5例HIV-1感染的参与者在2004年被纳入一个随访队列>84个月，并收到了拉米夫定为基础的一线ART方案。每6个月采集一次血液样本，以测量病毒载量和CD 4+细胞计数。超深度测序和系统发育分析被用来描述治疗失败的参与者的血浆RNA和细胞DNA之间HIV-1循环的准种多样性的动态特征（TF，n= 20）或病毒学抑制（VS，结果分析宿主内单核苷酸变异（iSNVs）及其突变等位基因频率的分布，发现大约65%的准种与宿主内的单核苷酸变异（iSNVs）共表达。iSNV的数量和频率更能代表宿主内HIV的多样性，并且比通过测量系统发育关联进行系统发育推断具有更好的普适性。此外，耐药相关突变（DRAM）积累到很高的水平，大大增加了TF患者的DRAM与总突变的比例。线性回归分析显示，紧急突变积累更快的TF患者相比，VS患者，在0.02突变/天/kb.ConclusionsBased的iSNV分析的速度，结果表明，在ART患者体内的HIV准种多样性的动态，并提供了一个新的洞察艾滋病毒的持久性和发展的DRAM。
ObjectivesHuman immunodeficiency virus (HIV) quasispecies diversity presents a large barrier to the eradication of HIV. The aim of this study was to investigate intrahost HIV quasispecies diversity and evolutionary patterns underpinning the mechanisms of viral pathogenesis during antiretroviral therapy (ART).MethodsForty-five participants with HIV-1 infection were enrolled in a follow-up cohort for >84 months in 2004, and received a lamivudine-based first-line ART regimen. Blood samples were collected every 6 months to measure viral load and CD4+cell count. Ultra-deep sequencing and phylogenetic analysis were used to characterize the dynamics governing quasispecies diversity of HIV-1 circulating between plasma RNA and cellular DNA of participants with treatment failure (TF,n= 20) or virologic suppression (VS,n= 25).ResultsAnalysis of the distribution of intrahost single-nucleotide variations (iSNVs) and their mutated allele frequencies revealed that approximately 65% of the quasispecies co-occurred in plasma HIV RNA and cellular DNA either before or after ART. The number and frequency of iSNVs are more representative of intrahost HIV diversity, and have better generalizability than phylogenetic inference by measurement of phylogenetic associations. Furthermore, drug-resistance-associated mutations (DRAMs) accumulated to high levels, dramatically increasing the DRAM-to-total-mutation ratio for TF patients. Linear regression analysis revealed that emergent mutations accumulated faster in TF patients compared with VS patients, at a rate of 0.02 mutations/day/kb.ConclusionsBased on iSNV analysis, the results demonstrate the dynamics of intrahost HIV quasispecies diversity in patients on ART, and provide a novel insight into the persistence of HIV and development of DRAMs.