Whole genome diversity of inherited chromosomally integrated HHV-6 derived from healthy individuals of diverse geographic origin.
Whole genome diversity of inherited chromosomally integrated HHV-6 derived from healthy individuals of diverse geographic origin.
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DOI：
10.1038/s41598-018-21645-x
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发表时间：
2018-02-22
影响因子：
4.6
通讯作者：
Santpere G
中科院分区：
文献类型：
--
作者：
Telford M;Navarro A;Santpere G
人类疱疹病毒6-A和-B(HHV-6A、HHV-6B)广泛存在于世界各地的人群中。这些病毒与多种疾病有关，如多发性硬化症、霍奇金淋巴瘤或脑炎。尽管需要了解这些病毒的遗传多样性和地理分层，但来自不同人群的完整病毒序列的可用性仍然有限。在这里，我们提出了来自不同地理来源的九个新的遗传的染色体整合的HHV-6序列，它们是通过对来自健康个体的淋巴母细胞系进行靶向DNA浓缩而产生的。结合现有的HHV-6序列，可以评估HHV-6A和HHV-6B的系统发育、重组模式和自然选择的特征。对物种内变异性的分析表明，A和B的多样性水平存在差异，并表明HHV-6B参考序列(Z29)是一个不常见的序列，这表明需要一个替代的参考序列。地理变异的迹象在HHV-6A中存在，并且更明确，而在HHV-6B中，它们似乎被重组部分掩盖了。最后，我们对蛋白质编码基因的选择特征进行了扫描，至少产生了6个基因(A和B物种分别为4个和2个)，显示加速进化的显著证据，以及1个基因显示HHV-6A的正选择证据。
Human herpesviruses 6-A and -B (HHV-6A, HHV-6B) are ubiquitous in human populations worldwide. These viruses have been associated with several diseases such as multiple sclerosis, Hodgkin’s lymphoma or encephalitis. Despite of the need to understand the genetic diversity and geographic stratification of these viruses, the availability of complete viral sequences from different populations is still limited. Here, we present nine new inherited chromosomally integrated HHV-6 sequences from diverse geographical origin which were generated through target DNA enrichment on lymphoblastoid cell lines derived from healthy individuals. Integration with available HHV-6 sequences allowed the assessment of HHV-6A and -6B phylogeny, patterns of recombination and signatures of natural selection. Analysis of the intra-species variability showed differences between A and B diversity levels and revealed that the HHV-6B reference (Z29) is an uncommon sequence, suggesting the need for an alternative reference sequence. Signs of geographical variation are present and more defined in HHV-6A, while they appear partly masked by recombination in HHV-6B. Finally, we conducted a scan for signatures of selection in protein coding genes that yielded at least 6 genes (4 and 2 respectively for the A and B species) showing significant evidence for accelerated evolution, and 1 gene showing evidence of positive selection in HHV-6A.
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