HIV-1 Subtype A Gag Variability and Epitope Evolution
HIV-1 Subtype A Gag Variability and Epitope Evolution
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DOI：
10.1371/journal.pone.0093415
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发表时间：
2014-06-03
期刊：
影响因子：
3.7
通讯作者：
Ali, Syed
中科院分区：
文献类型：
--
作者：
Abidi, Syed Hani;Kalish, Marcia L.;Ali, Syed
目的：本研究的目的是研究HIV-1亚型A在全球范围内的时间依赖性演变的过程中，特别是相对于免疫原性HIV gag epitopes.Methods的动态：我们使用了总共1,893 HIV-1亚型A gag序列代表一个时间轴从1985年到2010年，在非洲，欧洲和亚洲的19个不同的国家。通过最大似然树和贝叶斯Skyline图分析A亚型gag的系统发育关系及其流行动力学，根据G -> A置换和Shannon熵测量基因组变异，并检查HIV亚型A gag表位的时间依赖性进化。最后，确认观察全球报告的HIV亚型A序列，我们分析了我们的肯尼亚，巴基斯坦和阿富汗的队列，在两个队列特异性基因表位的变异性和HLA限制性概况的gag epitopes.Results的gag表位数据：最近的共同祖先的HIV亚型A流行病估计是1956 +/- 1。指数增长期大约从1980年开始，持续了大约7年，稳定了15年，下降了2-3年，然后从2004年左右再次稳定下来。在进化过程中，观察到基因组变异性逐渐增加，并在2005-2010年达到顶峰。结论：随着HIV A亚型在全球的流行，人群免疫遗传压力的变化可能对该亚型的免疫进化起到了一定的导向作用。这种趋势在HIV-1亚型A gag序列的基因组变异性和表位多样性中是明显的。
Objective: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes.Methods: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G -> A substitutions and Shannon entropy, and the time-dependent evolution of HIV subtype A gag epitopes was examined. Finally, to confirm observations on globally reported HIV subtype A sequences, we analysed the gag epitope data from our Kenyan, Pakistani, and Afghan cohorts, where both cohort-specific gene epitope variability and HLA restriction profiles of gag epitopes were examined.Results: The most recent common ancestor of the HIV subtype A epidemic was estimated to be 1956 +/- 1. A period of exponential growth began about 1980 and lasted for approximately 7 years, stabilized for 15 years, declined for 2-3 years, then stabilized again from about 2004. During the course of evolution, a gradual increase in genomic variability was observed that peaked in 2005-2010. We observed that the number of point mutations and novel epitopes in gag also peaked concurrently during 2005-2010.Conclusion: It appears that as the HIV subtype A epidemic spread globally, changing population immunogenetic pressures may have played a role in steering immune-evolution of this subtype in new directions. This trend is apparent in the genomic variability and epitope diversity of HIV-1 subtype A gag sequences.