Integrative functional genomics decodes herpes simplex virus 1

Integrative functional genomics decodes herpes simplex virus 1
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综合功能基因组学解码单纯疱疹病毒 1

DOI:
10.1038/s41467-020-15992-5
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发表时间:
2020
影响因子:
16.6
通讯作者:
Künzig
Künzig
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Whisnant;Adam W;Jürges;Christopher S;Hennig;Thomas;Emanuel;Prusty;Bhupesh;Rutkowski;Andrzej J;L'hernault;Djakovic;Göbel;Margarete;Döring;Kristina;Menegatti;Jennifer;Antrobus;Matheson;Nicholas J;Künzig

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单纯疱疹病毒1型(HSV-1)的80个开放阅读框(ORF)已被广泛研究了几十年。在这里,我们解开完整的病毒转录组和translatome裂解感染与碱基对分辨率的计算集成的多组学数据。我们确定了201个转录本和284个ORF,包括所有已知的和46个新的大ORF。这包括FDA批准的溶瘤病毒Imlygic中缺失的基因座中迄今未知的ORF。从单个基因位点表达的多种转录异构体解释了绝大多数ORF的翻译以及N-末端延伸(NTE)和截短。我们发现,非典型的起始密码子的NTE管理的亚细胞蛋白定位和包装的关键病毒调节因子和结构蛋白。我们扩展了目前的命名法,包括所有病毒基因产物,并提供了一个基因组浏览器,可视化所有获得的数据,从全基因组到单核苷酸分辨率。
The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution.
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