Niche adaptation and viral transmission of human papillomaviruses from archaic hominins to modern humans.
Niche adaptation and viral transmission of human papillomaviruses from archaic hominins to modern humans.
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DOI：
10.1371/journal.ppat.1007352
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发表时间：
2018-11
期刊：
影响因子：
6.7
通讯作者：
Burk RD
中科院分区：
文献类型：
--
作者：
Chen Z;DeSalle R;Schiffman M;Herrero R;Wood CE;Ruiz JC;Clifford GM;Chan PKS;Burk RD
现代人类起源于多个古人类种群和人类乳头瘤病毒（HPV）的多样性的最新发现表明了病毒宿主进化的复杂情况。为了评估HPV发病机制的起源，我们使用贝叶斯马尔可夫链蒙特卡罗框架估计了HPV 16变体的发生、时间和扩散。为了提高精确度，我们鉴定并表征了来自新世界和旧世界猴的非人灵长类乳头状瘤病毒，以建立分子钟模型。我们证明了灵长类乳头瘤病毒的特定宿主生态位适应，随后与灵长类宿主共进化至少4000万年。对212个HPV 16完整基因组和3582个部分序列的分析估计，大约50万年前，HPV 16变体（A和BCD谱系之间）与其最近的共同祖先的古老分歧，大致与古代尼安德特人和现代智人之间的分裂时间相吻合，并且比现代智人的分歧时间长近三倍。HPV 16 A谱系变异在目前非洲人群中的代表性明显不足，而A亚系在欧洲（A1-3）和亚洲（A4）人群中高度流行，表明在过去8万年中，通过多次杂交事件，从尼安德特人到现代非非洲人的病毒性传播。值得注意的是，与宫颈癌风险增加相关的人类白细胞抗原B*07：02和C*07：02等位基因代表了尼安德特人在现代欧亚人中的渗入区域。古老的人类-宿主-转换模型也得到了其他HPV变体的支持。小生境适应和病毒-宿主共趋异似乎影响乳头瘤病毒的发病机制。流行病学研究表明，某些致癌性人乳头瘤病毒（HPV）的持续感染是宫颈癌前病变和宫颈癌的主要原因。然而，我们对驱动特定类型HPV中病毒致瘤性的分化和出现的潜在进化机制的认识是不完整的。为了更好地了解致癌HPV的分子进化，我们从非人灵长类动物中分离病毒，评估乳头瘤病毒分子钟模型，并估计HPV 16和其他HPV类型变体与其最近共同祖先的分歧时间。灵长类PV宿主组织嗜性表明，作为致癌HPV进化的第一阶段，病毒对宿主生态系统的生态位适应。这些数据还提供了HPV变体与古代人类的古老共同分歧以及最近通过性交从尼安德特人传播到现代非非洲人的病毒传播的证据。了解乳头状瘤病毒的进化应该提供重要的生物学见解，并提出HPV诱导宫颈癌的机制，因为小生境适应而不是致癌性驱动病毒的适应性。
Recent discoveries on the origins of modern humans from multiple archaic hominin populations and the diversity of human papillomaviruses (HPVs) suggest a complex scenario of virus-host evolution. To evaluate the origin of HPV pathogenesis, we estimated the phylogeny, timing, and dispersal of HPV16 variants using a Bayesian Markov Chain Monte Carlo framework. To increase precision, we identified and characterized non-human primate papillomaviruses from New and Old World monkeys to set molecular clock models. We demonstrate specific host niche adaptation of primate papillomaviruses with subsequent coevolution with their primate hosts for at least 40 million years. Analyses of 212 HPV16 complete genomes and 3582 partial sequences estimated ancient divergence of HPV16 variants (between A and BCD lineages) from their most recent common ancestors around half a million years ago, roughly coinciding with the timing of the split between archaic Neanderthals and modern Homo sapiens, and nearly three times longer than divergence times of modern Homo sapiens. HPV16 A lineage variants were significantly underrepresented in present African populations, whereas the A sublineages were highly prevalent in European (A1-3) and Asian (A4) populations, indicative of viral sexual transmission from Neanderthals to modern non-African humans through multiple interbreeding events in the past 80 thousand years. Remarkably, the human leukocyte antigen B*07:02 and C*07:02 alleles associated with increased risk in cervix cancer represent introgressed regions from Neanderthals in present-day Eurasians. The archaic hominin-host-switch model was also supported by other HPV variants. Niche adaptation and virus-host codivergence appear to influence the pathogenesis of papillomaviruses. Epidemiologic studies have demonstrated that persistent infection of select oncogenic human papillomaviruses (HPVs) is the main cause of cervix precancer and cancer. Nevertheless, our knowledge of the underlying evolutionary mechanisms driving the divergence and emergence of viral oncogenicity in specific types of HPVs is incomplete. To better understand the molecular evolution of oncogenic HPVs, we isolated viruses from non-human primates, evaluated papillomavirus molecular clock models, and estimated the divergence times of HPV16 and other HPV type variants from their most recent common ancestors. Primate PV-host tissue tropisms indicated niche adaptation of viruses to host ecosystems as the first stage of the evolution of oncogenic HPVs. The data also provided evidence of ancient codivergence of HPV variants with archaic hominins and recent viral transmission from Neanderthals to modern non-African humans through sexual intercourse. Understanding the evolution of papillomaviruses should provide important biological insights and suggest mechanisms underlying HPV-induced cervical cancer, since niche adaptation rather than oncogenicity drives viral fitness.
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