National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Canada.
PLoS One. 2012;7(5):e36933. doi: 10.1371/journal.pone.0036933. Epub 2012 May 31.
Host immune selection pressure influences the development of mutations that allow for HIV escape. Mutation patterns induced in HIV by the human leukocyte antigen (HLA) are HLA-allele specific. As ethnic groups have distinct and characteristic HLA allele frequencies, we can expect divergent viral evolution within ethnicities. Here, we have sequenced and analyzed the HIV pol gene from 1248 subtype B infected, treatment-naïve individuals in Canada. Phylogenetic analysis showed no separation between pol sequences from five self-identified ethnic groups, yet fixation index (F(ST)) values showed significant divergence between ethnicities. A total of 17 amino acid sites showed an ethnic-specific fixation pattern (0.015<F(ST) <0.060, p<0.01), and 27 codons were inferred to be under positive selection (p<0.01), with each set of sites strongly associated with HLA sites (p = 1.78×10(-6) and p = 1.91×10(-7), respectively). Within the pol gene, eight sites under HLA selective pressure were correlated with ethnicity, indicating 'adaptive divergence' between the groups studied. Our findings highlight challenges in HIV vaccine design in ethnically diverse countries with subtype B epidemics.
宿主免疫选择压力影响允许 HIV 逃逸的突变的发展。人类白细胞抗原 (HLA) 诱导的 HIV 中的突变模式是 HLA 等位基因特异性的。由于不同的族群具有独特的 HLA 等位基因频率，我们可以预期在族群内会出现不同的病毒进化。在这里，我们对来自加拿大 1248 名未经治疗的 B 型亚型 HIV 感染者的 HIV pol 基因进行了测序和分析。系统进化分析显示，来自五个自我认定的族群的 pol 序列没有分离，但固定指数 (F(ST)) 值显示族群之间存在显著的差异。共有 17 个氨基酸位点显示出族群特异性固定模式（0.015<F(ST)<0.060，p<0.01），27 个密码子被推断为受到正选择（p<0.01），每组位点都与 HLA 位点强烈相关（p=1.78×10(-6) 和 p=1.91×10(-7)）。在 pol 基因中，八个受到 HLA 选择压力的位点与族群有关，表明研究群体之间存在“适应性分歧”。我们的研究结果强调了在具有 B 型流行的人种多样化国家设计 HIV 疫苗所面临的挑战。
