Abidi Syed Hani, Kalish Marcia L, Abbas Farhat, Rowland-Jones Sarah, Ali Syed
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Vanderbilt Institute of Global health, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One. 2014 Jun 3;9(6):e93415. doi: 10.1371/journal.pone.0093415. eCollection 2014.
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.
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.
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.
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.
本研究旨在在全球范围内研究HIV-1 A亚型随时间的演变过程，尤其是免疫原性HIV gag表位的动态变化。
我们总共使用了1893条HIV-1 A亚型gag序列，这些序列代表了从1985年到2010年的时间线，涵盖了非洲、欧洲和亚洲的19个不同国家。通过最大似然树和贝叶斯天际线图分析了A亚型gag的系统发育关系及其流行动态，以G→A替换和香农熵来衡量基因组变异性，并研究了HIV A亚型gag表位随时间的演变。最后，为了证实对全球报告的HIV A亚型序列的观察结果，我们分析了来自肯尼亚、巴基斯坦和阿富汗队列的gag表位数据，研究了队列特异性基因表位变异性和gag表位的HLA限制谱。
估计HIV A亚型流行的最近共同祖先为1956年±1年。指数增长期始于1980年左右，持续约7年，稳定15年，下降2 - 3年，然后从2004年左右再次稳定。在进化过程中，观察到基因组变异性逐渐增加，在2005 - 2010年达到峰值。我们还观察到gag中的点突变和新表位数量在2005 - 2010年期间也同时达到峰值。
随着HIV A亚型在全球范围内传播，不断变化的人群免疫遗传压力似乎可能在引导该亚型的免疫进化走向新方向方面发挥了作用。这种趋势在HIV-1 A亚型gag序列的基因组变异性和表位多样性中很明显。
