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Evolutionary analysis of exogenous and integrated HHV-6A/HHV-6B populations
Virus Evolution ( IF 5.3 ) Pub Date : 2020-01-01 , DOI: 10.1093/ve/veaa035
Diego Forni 1 , Rachele Cagliani 1 , Mario Clerici 2, 3 , Uberto Pozzoli 1 , Manuela Sironi 1
Affiliation  

Abstract Human betaherpesviruses 6A and 6B (HHV-6A and HHV-6B) are highly prevalent in human populations. The genomes of these viruses can be stably integrated at the telomeres of human chromosomes and be vertically transmitted (inherited chromosomally integrated HHV-6A/HHV-6B, iciHHV-6A/iciHHV-6B). We reconstructed the population structures of HHV-6A and HHV-6B, showing that HHV-6A diverged less than HHV-6B genomes from the projected common ancestral population. Thus, HHV-6B genomes experienced stronger drift, as also supported by calculation of nucleotide diversity and Tajima’s D. Analysis of ancestry proportions indicated that HHV-6A exogenous viruses and iciHHV-6A derived most of their genomes from distinct ancestral sources. Conversely, ancestry proportions were similar in exogenous HHV-6B viruses and iciHHV-6B. In line with previous indications, this suggests the distinct exogenous viral populations that originated iciHHV-6B in subjects with European and Asian ancestry are still causing infections in the corresponding geographic areas. Notably, for both iciHHV-6A and iciHHV-6B, we found that European and American sequences tend to have high proportions of ancestry from viral populations that experienced considerable drift, suggesting that they underwent one or more bottlenecks followed by population expansion. Finally, analysis of HHV-6B exogenous viruses sampled in Japan indicated that proportions of ancestry components of most of these viruses are different from the majority of those sampled in the USA. More generally, we show that, in both viral species, both integrated and exogenous viral genomes have different ancestry components, partially depending on geographic location. It would be extremely important to determine whether such differences account for the diversity of HHV-6A/HHV-6B-associated clinical symptoms and epidemiology. Also, the sequencing of additional exogenous and integrated viral genomes will be instrumental to confirm and expand our conclusions, which are based on a relatively small number of genomes, sequenced with variable quality, and with unequal sampling in terms of geographic origin.

中文翻译:

外源性和整合性 HHV-6A/HHV-6B 种群的进化分析

摘要 人类β疱疹病毒 6A 和 6B(HHV-6A 和 HHV-6B)在人群中高度流行。这些病毒的基因组可以稳定地整合在人类染色体的端粒上并可以垂直传播(遗传染色体整合HHV-6A/HHV-6B、iciHHV-6A/iciHHV-6B)。我们重建了 HHV-6A 和 HHV-6B 的种群结构,表明 HHV-6A 与 HHV-6B 基因组的差异小于预测的共同祖先种群。因此,HHV-6B 基因组经历了更强的漂移,这也得到了核苷酸多样性计算和 Tajima's D 的支持。祖先比例分析表明 HHV-6A 外源病毒和 iciHHV-6A 的大部分基因组来自不同的祖先来源。相反,外源性 HHV-6B 病毒和 iciHHV-6B 的祖先比例相似。与之前的迹象一致,这表明源自欧洲和亚洲血统受试者的 iciHHV-6B 的独特外源病毒种群仍在相应地理区域引起感染。值得注意的是,对于 iciHHV-6A 和 iciHHV-6B,我们发现欧洲和美国的序列往往具有来自经历了相当大漂移的病毒种群的高比例祖先,这表明它们经历了一个或多个瓶颈,然后是种群扩张。最后,对日本采样的 HHV-6B 外源病毒的分析表明,大多数这些病毒的祖先成分比例与美国采样的大多数不同。更一般地说,我们表明,在两种病毒物种中,整合的和外源的病毒基因组都有不同的祖先成分,部分取决于地理位置。确定这种差异是否解释了 HHV-6A/HHV-6B 相关临床症状和流行病学的多样性将是极其重要的。此外,额外的外源性和整合病毒基因组的测序将有助于确认和扩展我们的结论,这些结论基于相对较少的基因组,测序质量各不相同,并且在地理来源方面采样不均。
更新日期:2020-01-01
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