The First Endogenous Herpesvirus, Identified in the Tarsier Genome, and Novel Sequences from Primate Rhadinoviruses and Lymphocryptoviruses
The First Endogenous Herpesvirus, Identified in the Tarsier Genome, and Novel Sequences from Primate Rhadinoviruses and Lymphocryptoviruses
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DOI：
10.1371/journal.pgen.1004332
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发表时间：
2014-06-01
期刊：
影响因子：
4.5
通讯作者：
Katzourakis, Aris
中科院分区：
文献类型：
--
作者：
Aswad, Amr;Katzourakis, Aris
疱疹病毒科是一个由大型且复杂的病原体组成的多样化家族，其基因组极其难以测序。对于临床样本，以及首次对病毒、宿主或两者基因组进行测序时尤其如此。尽管已知疱疹病毒偶尔会整合到宿主基因组中，并且也可以以孟德尔方式遗传，但值得注意的是，它们不存在于由内源病毒元件（EVE）组成的基因组化石记录中。在这里，我们结合古病毒学和宏基因组方法来探索哺乳动物基因组的病毒组成多样性并寻找内源性疱疹病毒。我们描述了来自菲律宾眼镜猴基因组的第一个内源性疱疹病毒，属于玫瑰病毒属，并描述了其高度缺陷的基因组，该基因组被整合并侧翼有明确的宿主DNA。从指猴基因组的草图组装中，我们使用生物信息学工具揭示了一种新型病毒的超过 100,000 bp，这是第一种狐猴伽马疱疹病毒，与卡波西肉瘤相关病毒密切相关。我们还鉴定了 Paniscus 淋巴隐病毒 1 型（相当于人类 Epstein-Barr 病毒的倭黑猩猩）的 58 个基因。对于每种病毒，我们通过与已知病毒亲属的比较分析来推测基因功能。最值得注意的是，来自基因内容和系统发育的证据表明，指猴序列代表了已知的最基本的病毒，并表明致瘤性疱疹病毒自白垩纪晚期出现以来一直在感染灵长类动物。总体而言，这些数据表明，尽管疱疹病毒的基因组非常大，但其基因组化石记录仍然存在，并扩展了疱疹病毒科的已知多样性，这将有助于发病机制的表征。我们的分析方法说明了进化方法与宏基因组学、遗传学和古病毒学交叉的好处。
Herpesviridae is a diverse family of large and complex pathogens whose genomes are extremely difficult to sequence. This is particularly true for clinical samples, and if the virus, host, or both genomes are being sequenced for the first time. Although herpesviruses are known to occasionally integrate in host genomes, and can also be inherited in a Mendelian fashion, they are notably absent from the genomic fossil record comprised of endogenous viral elements (EVEs). Here, we combine paleovirological and metagenomic approaches to both explore the constituent viral diversity of mammalian genomes and search for endogenous herpesviruses. We describe the first endogenous herpesvirus from the genome of the Philippine tarsier, belonging to the Roseolovirus genus, and characterize its highly defective genome that is integrated and flanked by unambiguous host DNA. From a draft assembly of the aye-aye genome, we use bioinformatic tools to reveal over 100,000 bp of a novel rhadinovirus that is the first lemur gammaherpesvirus, closely related to Kaposi's sarcoma-associated virus. We also identify 58 genes of Pan paniscus lymphocryptovirus 1, the bonobo equivalent of human Epstein-Barr virus. For each of the viruses, we postulate gene function via comparative analysis to known viral relatives. Most notably, the evidence from gene content and phylogenetics suggests that the aye-aye sequences represent the most basal known rhadinovirus, and indicates that tumorigenic herpesviruses have been infecting primates since their emergence in the late Cretaceous. Overall, these data show that a genomic fossil record of herpesviruses exists despite their extremely large genomes, and expands the known diversity of Herpesviridae, which will aid the characterization of pathogenesis. Our analytical approach illustrates the benefit of intersecting evolutionary approaches with metagenomics, genetics and paleovirology.