Convergence and divergence in the evolution of the APOBEC3G-Vif interaction reveal ancient origins of simian immunodeficiency viruses.
Convergence and divergence in the evolution of the APOBEC3G-Vif interaction reveal ancient origins of simian immunodeficiency viruses.
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DOI：
10.1371/journal.ppat.1003135
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发表时间：
2013-01
期刊：
影响因子：
6.7
通讯作者：
Emerman M
中科院分区：
文献类型：
--
作者：
Compton AA;Emerman M
自然传播的慢病毒在今天的非洲灵长类物种中大量存在，但它们的来源和在宿主之间传播的历史仍然不清楚。为了更好地了解灵长类慢病毒的年龄，我们分析了灵长类基因组，以寻找慢病毒驱动的进化的特征。具体地说，我们研究了寄主限制因子APOBEC3G(A3G)在东半球猴(OWM)物种中的适应性进化。我们在多个灵长类动物谱系中发现了A3G的反复突变，这些突变决定了慢病毒辅助蛋白Vif对拮抗的敏感性。使用广泛的SIV Vif分离株，我们证明了OWM A3G的自然变异赋予了对Vif介导的降解的抵抗力，这表明宿主因子的适应性变体是在至少500-600万年前(MYA)暴露于致病慢病毒(MYA)时选择的。此外，在OWM的分歧型Colobinae亚家族成员中，A3G中出现的至少12个MYA的多残基插入事件阻止了Vif的活性，这表明SIV的起源甚至更古老。此外，对与Colobinae猴子相关的慢病毒的分析表明，A3G-Vif相互作用的界面发生了变化，并导致了第二次遗传冲突。我们对病毒驱动的进化的分析描述了在一百万年的时间尺度上，猿类灵长类动物和慢病毒之间古老而持续的遗传冲突。20世纪末艾滋病的出现促使研究人员更好地了解病毒的进化史和控制其传播的因素。大流行性人类免疫缺陷病毒1型(HIV-1)目前感染着全球3400万人，它是在黑猩猩和人类之间传播慢病毒后出现的。越来越多的明显非致病性、物种特有的菌株现在已经在数十种非洲灵长类动物身上表现出特征，这表明灵长类慢病毒比最初认为的更古老，分布更广泛。为了估计灵长类动物和慢病毒共存的程度，我们在分子水平上检查了宿主和病毒之间的相互作用，并跟踪了其随进化时间的动态变化。我们报告说，免疫因子APOBEC3G与慢病毒辅助基因vif一起进化，使我们能够在深层次和浅层次上将宿主进化的实例与慢病毒感染的实例相关联。具体地说，我们表明Vif针对的APOBEC3G区域在独立的灵长类谱系中正在适应性地多样化，这表明慢病毒已有数百万年的历史。我们的研究表明，虽然灵长类慢病毒可能对人类健康产生现代后果，但它们起源于我们的非人类灵长类亲属。
Naturally circulating lentiviruses are abundant in African primate species today, yet their origins and history of transmitting between hosts remain obscure. As a means to better understand the age of primate lentiviruses, we analyzed primate genomes for signatures of lentivirus-driven evolution. Specifically, we studied the adaptive evolution of host restriction factor APOBEC3G (A3G) in Old World Monkey (OWM) species. We find recurrent mutation of A3G in multiple primate lineages at sites that determine susceptibility to antagonism by the lentiviral accessory protein Vif. Using a broad panel of SIV Vif isolates, we demonstrate that natural variation in OWM A3G confers resistance to Vif-mediated degradation, suggesting that adaptive variants of the host factor were selected upon exposure to pathogenic lentiviruses at least 5–6 million years ago (MYA). Furthermore, in members of the divergent Colobinae subfamily of OWM, a multi-residue insertion event in A3G that arose at least 12 MYA blocks the activity of Vif, suggesting an even more ancient origin of SIV. Moreover, analysis of the lentiviruses associated with Colobinae monkeys reveal that the interface of the A3G-Vif interaction has shifted and given rise to a second genetic conflict. Our analysis of virus-driven evolution describes an ancient yet ongoing genetic conflict between simian primates and lentiviruses on a million-year time scale. The emergence of AIDS in the late 20th century has provoked studies to better understand the evolutionary history of viruses and the factors that govern their spread. Pandemic human immunodeficiency virus-type 1 (HIV-1), which currently infects 34 million people worldwide, emerged following the transmission of a lentivirus between chimpanzees and humans. A growing list of apparently nonpathogenic, species-specific strains has now been characterized in dozens of African primates, suggesting that primate lentiviruses are older and more widespread than originally thought. To estimate the extent to which primates and lentiviruses have coexisted, we examined the interaction between host and virus on a molecular level and tracked its dynamics over evolutionary time. We report that the immunity factor APOBEC3G is evolving in tandem with the lentiviral accessory gene vif, allowing us to associate instances of host evolution with instances of lentivirus infection in deep and shallow timescales. Specifically, we show that the region of APOBEC3G targeted by Vif is adaptively diversifying in independent primate lineages in a manner that suggests that lentiviruses are millions of years old. Our study reveals that, while primate lentiviruses may have modern consequences for human health, they have ancient origins in our non-human primate relatives.
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