Forni Diego, Cagliani Rachele, Clerici Mario, Pozzoli Uberto, Sironi Manuela
Bioinformatics, Scientific Institute IRCCS E. MEDEA, 23842 Bosisio Parini, Lecco, Italy.
Department of Physiopathology and Transplantation, University of Milan, 20090 Milan, Italy.
Virus Evol. 2020 Apr 30;6(1):veaa035. doi: 10.1093/ve/veaa035. eCollection 2020 Jan.
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 . 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.
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稳定整合于人类染色体的端粒处，并进行垂直传播（遗传性染色体整合HHV - 6A/HHV - 6B，iciHHV - 6A/iciHHV - 6B）。我们重建了HHV - 6A和HHV - 6B的种群结构，结果表明，与推测的共同祖先种群相比，HHV - 6A基因组的分化程度低于HHV - 6B基因组。因此，HHV - 6B基因组经历了更强的漂变，核苷酸多样性计算和 Tajima's 分析也支持这一点。祖先比例分析表明，HHV - 6A外源性病毒和iciHHV - 6A的大部分基因组来源于不同的祖先。相反，外源性HHV - 6B病毒和iciHHV - 6B的祖先比例相似。与之前的研究结果一致，这表明起源于欧洲和亚洲血统个体的iciHHV - 6B的不同外源性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程度漂变的病毒种群的高比例祖先，这表明它们经历了一次或多次瓶颈效应，随后种群扩张。最后，对在日本采集的HHV - 6B外源性病毒的分析表明，这些病毒中大多数的祖先成分比例与在美国采集的大多数病毒不同。更普遍地说，我们表明，在这两种病毒中，整合型和外源性病毒基因组都有不同的祖先成分，部分取决于地理位置。确定这些差异是否解释了HHV - 6A/HHV - 6B相关临床症状和流行病学的多样性将极其重要。此外，对更多外源性和整合型病毒基因组进行测序将有助于确认和扩展我们的结论，我们的结论基于数量相对较少、测序质量参差不齐且地理来源采样不均衡的基因组。
