Investigating signs of recent evolution in the pool of proviral HIV type 1 DNA during years of successful HAART
Investigating signs of recent evolution in the pool of proviral HIV type 1 DNA during years of successful HAART
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DOI：
10.1089/aid.2006.0089
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发表时间：
2007-01-01
影响因子：
1.5
通讯作者：
Katzenstein, Terese L.
中科院分区：
文献类型：
--
作者：
Mens, Helene;Pedersen, Anders G.;Katzenstein, Terese L.
为了阐明 1 型人类免疫缺陷病毒 (HIV1) 持久储存库的性质，我们研究了成功接受 HAART 的患者前病毒 DNA 库的近期进化迹象。从 57 名患者分离的 PBMC 中收集了对应于 HIV-1 env 基因的 C2-V3-C3 区域的前病毒 DNA。 “共识”（57 名患者）和克隆（7 名患者）序列均是从 24 个月期间的五个时间点获得的。主要的计算策略是使用最大似然将一组替代系统发育模型拟合到克隆数据，然后确定对暗示时间点之间进化的模型的支持。使用 Akaike 信息准则 (AIC) 和 Akaike 权重评估模型拟合和模型选择不确定性。还使用一系列系统发育技术对共有序列数据进行了分析，以确定是否存在表明正在进行的复制和进化的时间趋势。总之，用这里使用的方法不可能在批量测序或克隆数据中检测到持续进化的明确迹象，但我们的结果可能与一些患者中存档的 HIV 基因组的局部表达一致。有趣的是，终止密码子存在于几个独立克隆和跨患者的相同两个位置。模拟研究表明，这种现象可以解释为平行进化的结果，并且某些位点本质上更有可能进化成终止密码子。
In order to shed light on the nature of the persistent reservoir of human immunodeficiency virus type 1 (HIV1), we investigated signs of recent evolution in the pool of proviral DNA in patients on successful HAART. Pro-viral DNA, corresponding to the C2-V3-C3 region of the HIV-1 env gene, was collected from PBMCs isolated from 57 patients. Both "consensus" ( 57 patients) and clonal ( 7 patients) sequences were obtained from five time points spanning a 24-month period. The main computational strategy was to use maximum likelihood to fit a set of alternative phylogenetic models to the clonal data, and then determine the support for models that imply evolution between time points. Model fit and model-selection uncertainty was assessed using the Akaike information criterion (AIC) and Akaike weights. The consensus sequence data was also analyzed using a range of phylogenetic techniques to determine whether there were temporal trends indicating ongoing replication and evolution. In summary, it was not possible to detect definitive signs of ongoing evolution in either the bulk-sequenced or the clonal data with the methods employed here, but our results could be consistent with localized expression of archival HIV genomes in some patients. Interestingly, stop-codons were present at the same two positions in several independent clones and across patients. Simulation studies indicated that this phenomenon could be explained as the result of parallel evolution and that some sites were inherently more likely to evolve into stop codons.