Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of the human population. They encompass large genomes and our understanding of their protein coding potential is far from complete. Here, we employ ribosome-profiling and systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds of new open reading frames (ORFs), including upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. By integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs conserved across betaherpesviruses and we show uORFs are enriched in late viral genes. We identified three highly abundant HHV-6 encoded long non-coding RNAs, one of which generates a non-polyadenylated stable intron appearing to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features conserved between betaherpesviruses, providing a rich resource for future functional studies.

中文翻译：

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人类疱疹病毒6A和6B基因组的全面注释揭示了新颖且保守的基因组特征

人疱疹病毒6（HHV-6）A和B是普遍存在的β疱疹病毒，感染了大多数人口。它们涵盖了大型基因组，而我们对其蛋白质编码潜力的理解还远远不够。在这里，我们采用核糖体谱分析和系统的转录本分析来实验确定HHV-6翻译产物。我们确定了数百个新的开放阅读框（ORF），包括上游ORF（uORF）和内部ORF（iORF），生成了完整的HHV-6蛋白质组图谱。通过整合来自原型β疱疹病毒，人类巨细胞病毒的系统数据，我们发现了跨越β疱疹病毒保守的众多uORF和iORF，并且我们证明uORF富含晚期病毒基因。我们鉴定了三个高度丰富的HHV-6编码的长非编码RNA，其中之一产生非聚腺苷酸稳定的内含子，似乎是β疱疹病毒的保守特征。总的来说，我们的工作揭示了HHV-6基因组的复杂性，并突出了β疱疹病毒之间保守的新颖特征，为将来的功能研究提供了丰富的资源。