Alphaherpesviruses, as large double-stranded DNA viruses, were long considered to be genetically stable and to exist in a homogeneous state. Recently, the proliferation of high-throughput sequencing (HTS) and bioinformatics analysis has expanded our understanding of herpesvirus genomes and the variations found therein. Recent data indicate that herpesviruses exist as diverse populations, both in culture and in vivo, in a manner reminiscent of RNA viruses. In this review, we discuss the past, present, and potential future of alphaherpesvirus genomics, including the technical challenges that face the field. We also review how recent data has enabled genome-wide comparisons of sequence diversity, recombination, allele frequency, and selective pressures, including those introduced by cell culture. While we focus on the human alphaherpesviruses, we draw key insights from related veterinary species and from the beta- and gamma-subfamilies of herpesviruses. Promising technologies and potential future directions for herpesvirus genomics are highlighted as well, including the potential to link viral genetic differences to phenotypic and disease outcomes.

中文翻译：

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阿尔法疱疹病毒基因组学：过去、现在和未来。

α疱疹病毒作为大型双链DNA病毒，长期以来被认为是遗传稳定的并且以均质状态存在。最近，高通量测序（HTS）和生物信息学分析的普及扩大了我们对疱疹病毒基因组及其中发现的变异的了解。最近的数据表明，疱疹病毒在培养物和体内均以不同的种群存在，其方式类似于 RNA 病毒。在这篇综述中，我们讨论了α疱疹病毒基因组学的过去、现在和潜在的未来，包括该领域面临的技术挑战。我们还回顾了最近的数据如何实现序列多样性、重组、等位基因频率和选择压力（包括细胞培养引入的压力）的全基因组比较。虽然我们专注于人类 α 疱疹病毒，但我们从相关兽医物种以及疱疹病毒的 β 和 γ 亚科中汲取了重要见解。还强调了疱疹病毒基因组学的有前途的技术和潜在的未来方向，包括将病毒遗传差异与表型和疾病结果联系起来的潜力。