Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Il 61801, USA.
BMC Evol Biol. 2012 Dec 6;12:237. doi: 10.1186/1471-2148-12-237.
HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1.
SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding.
We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.
HIV-1 源自于从黑猩猩向人类群体中多次独立转移的猿猴免疫缺陷病毒（SIV）毒株。我们假设，在大流行之前，中西非的人类群体可能已经接触过 SIV，而之前的爆发可能已经选择了对免疫缺陷病毒具有遗传抗性的人群。为了验证这一假设，我们研究了生活在中非黑猩猩亚种（Pan troglodytes troglodytes）地理范围内的社区中的比亚卡西部俾格米人（Biaka Western Pygmies）的基因组，这些社区携带了与 HIV-1 祖先相关的 SIV 毒株。
比亚卡人的单核苷酸多态性（SNP）基因型与那些历史上居住在 P. t. troglodytes 范围之外的非洲人类群体（包括姆布蒂东部俾格米人）进行了比较。与 HIV 感染或发病机制相关的基因的基因组位置比较了显示选择特征的基因组区域。在比亚卡人中，检测到 CUL5 存在强烈的选择信号，CUL5 编码 vif 介导的 APOBEC3 降解途径的一个组成部分。在比亚卡人中，一种对艾滋病进展具有保护作用的 CUL5 等位基因已经固定。在 TRIM5 中检测到一个选择信号，TRIM5 编码一种 HIV 进入后限制因子。与其他非洲人群相比，比亚卡人中的 TRIM5 保护性错义突变的频率最高，APOBEC3G 的保护性等位基因也是如此，APOBEC3G 编码一种抗 HIV-1 限制因子。APOBEC3H、CXCR6 和 HLA-C 对 HIV-1 的保护性等位基因在比亚卡人中的频率高于姆布蒂人中。比亚卡人的 TSG101 基因组显示出强烈的选择信号，TSG101 是 HIV-1 病毒出芽的抑制剂。
我们在与 HIV-1 感染或进展相关的多个基因中发现了对比亚卡人具有保护作用的等位基因或选择证据。也有报道称，俾格米人携带了对 CCR5 和 CCL3L1 基因具有保护作用的 HIV-1 基因型。我们的假设是，HIV-1 可能已经塑造了中西非一些人类群体的基因组，这似乎值得进一步研究。
