Evidence for CTL-mediated selection of Tat and Rev mutants after the onset of the asymptomatic period during HIV type 1 infection
Evidence for CTL-mediated selection of Tat and Rev mutants after the onset of the asymptomatic period during HIV type 1 infection
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DOI：
10.1089/aid.2006.22.1283
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发表时间：
2006-12-01
影响因子：
1.5
通讯作者：
Verrier, B.
中科院分区：
文献类型：
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作者：
Guillon, C.;Stankovic, K.;Verrier, B.
随着时间的推移，HIV-1序列的进化是选择逃脱宿主免疫反应的突变变体的结果，或者是随着病毒复制增加而产生的突变变体，或者两者兼而有之。我们研究了这两个选择过程对四个个体的TAT和REV调控基因序列整体进化的贡献，时间范围从血清转换之前到稳定的无症状感染。在对每个样本每个基因至少15个克隆进行测序后，我们分析了根据这些患者的MHC-I单倍型预测的MHC-I基序的序列进化。对于每个已鉴定的TAT序列，我们在体外转录激活试验中测试了相应编码蛋白的活性。我们的结果表明，这些个体的TAT和REV序列的进化可以通过MHC-I表位的突变逃逸来解释，并且没有取代病毒群体中原始序列的突变与TAT活性的增加或减少有关。CTL介导的选择似乎是HIV-1感染早期调控基因序列进化的重要决定因素。
The evolution of HIV-1 sequences over time is the result of the selection of mutant variants that have escaped from host immune responses or the outgrowth of mutants with increased viral replication, or both. We investigated the contribution of both selection processes to the overall evolution of the Tat and Rev regulatory gene sequences from four individuals, ranging in time from just prior to seroconversion to stable asymptomatic infection. After sequencing at least 15 clones per sample per gene, we analyzed the sequence evolution of the MHC-I motifs that were predicted from the MHC-I haplotypes of these patients. For each identified Tat sequence, we tested the activity of the corresponding encoded protein in a transactivation assay in vitro. Our results suggest that the evolution of the Tat and Rev sequences from these individuals can be explained by mutational escape of the MHC-I epitopes and that no mutations that replaced the original sequences in the viral population are associated with either an increase or decrease in Tat activity. CTL-mediated selection appears to be an important determinant of HIV-1 regulatory gene sequence evolution during the early stages of infection.