Evidence for positive selection driving the evolution of HIV-1 env under potent antiviral therapy
Evidence for positive selection driving the evolution of HIV-1 env under potent antiviral therapy
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DOI：
10.1006/viro.2000.0887
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发表时间：
2001-06-05
期刊：
影响因子：
3.7
通讯作者：
Brown, AJL
中科院分区：
文献类型：
--
作者：
Frost, SDW;G端nthard, HF;Brown, AJL
在接受强效抗逆转录病毒治疗的HIV感染者中，由于这些细胞的寿命长，持续复制补充了该群体，或两者兼而有之，因此可以在治疗数年后从潜伏感染的细胞中分离出活病毒。我们分析了从6例患者中分离的HIV-1 env基因的Vs区域，这些患者接受了2年有效的抗逆转录病毒治疗，但病毒抑制没有明显失败。我们发现，在两名（可能是三名）患者中，基线病毒和从感染细胞中分离的病毒之间的序列变化持续2年，导致正向选择驱动适应性进化，发生在治疗之前或治疗期间。我们的分析表明，低水平的复制，尽管缺乏耐药性，由于药物避难所网站，或低水平的持续复制的存在下，在治疗过程中的选择性环境的改变，可能是由于艾滋病毒特异性免疫反应性下降或靶细胞池的变化。在一名患者中，基线血浆和治疗期间分离的感染细胞之间的遗传差异可能反映了这些持久性细胞群中的一些的长半衰期和治疗前发生的病毒亚群的差异。(C)北京：科学出版社.
In HIV-infected individuals treated with potent antiretroviral therapy, viable virus can be isolated from latently infected cells several years into therapy, due to the long life of these cells, ongoing replication replenishing this population, or both. We have analysed the Vs region of the HIV-1 env gene isolated from six patients who have undergone 2 years of potent antiretroviral therapy without frank failure of viral suppression. We show that in two (and possibly three) patients, the sequence changes between baseline virus and virus isolated from infected cells persisting 2 years into infection result from positive selection driving adaptive evolution, occurring either prior to or during therapy. Our analyses suggest low-level replication despite absence of drug resistance due to drug sanctuary sites, or to low-level ongoing replication in the presence of alterations in the selective environment during therapy, perhaps due to a decline in HIV-specific immune responsiveness or changes in target cell pools. In one patient, genetic divergence between baseline plasma and infected cells isolated during therapy may reflect the long half-life of some of these persistent cell populations and the divergence of viral subpopulations that occurred prior to therapy. (C) 2001 Academic Press.