Medical College, Aga Khan University, Karachi, Pakistan.
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
PLoS One. 2022 May 10;17(5):e0267130. doi: 10.1371/journal.pone.0267130. eCollection 2022.
Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant HIV-1 protein, we performed a comparative analysis of the CRF01_AE gag protein's time-dependent changes and evolution. A total of 3105 HIV-1 CRF01_AE gag sequences representing 17 countries from the timeline 1990-2017 were obtained. The sequences' phylogenetic relationship and epidemic dynamics were analyzed through a Maximum Likelihood tree and Bayesian Skyline plot, respectively. Genomic variability was measured through Shannon entropy and time-dependent immunoevolution was analyzed using changes in proteasomal degradation pattern, cytotoxic T lymphocytes (CTL) epitopes, and Human leukocyte antigens (HLA) restriction profile. The most recent common ancestor of the HIV CRF01_AE epidemic was estimated to be 1974±1. A period of exponential growth in effective population size began in 1982, fluctuated, and then stabilized in 1999. Genetic variability (entropy) consistently increased, however, epitope variability remained comparable; the highest number of novel CTL epitopes were present in 1995-1999, which were lost over time. The spread of the HIV-1 CRF01_AE epidemic is predominant in countries within Asia. Population immunogenetic pressures in the region may have contributed to the initial changes and following adaptation/stabilization of epitope diversity within gag sequences.
目前，人们对人类免疫缺陷病毒 1 型（HIV-1）循环重组形式（CRF）01_AE 的时间依赖性进化知之甚少，这是一种与全球 HIV-1 流行相关的主要重组形式。由于 gag 是高度免疫显性的 HIV-1 蛋白，我们对 CRF01_AE gag 蛋白的时间依赖性变化和进化进行了比较分析。共获得了代表 1990 年至 2017 年 17 个国家的 3105 个 HIV-1 CRF01_AE gag 序列。通过最大似然树和贝叶斯天空线图分别分析了序列的系统发育关系和流行动态。通过香农熵衡量基因组变异性，并通过分析蛋白酶体降解模式、细胞毒性 T 淋巴细胞（CTL）表位和人类白细胞抗原（HLA）限制谱的变化来分析时间依赖性免疫进化。HIV CRF01_AE 流行的最近共同祖先估计为 1974±1。1982 年开始，有效种群大小呈指数增长，波动后于 1999 年稳定。遗传变异性（熵）持续增加，但表位变异性保持可比；1995-1999 年出现的新 CTL 表位数量最多，随着时间的推移逐渐消失。HIV-1 CRF01_AE 流行的传播主要集中在亚洲国家。该地区人群免疫遗传压力可能导致 gag 序列中最初的变化以及随后的表位多样性适应/稳定。
