Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-15992-5
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Funding
- European Research Council [ERC-2016-CoG 721016 - HERPES]
- MRC [CSF G1002523, MR/P008801/1]
- Wellcome Trust [PRF 210688/Z/18/Z]
- DFG [1275/6-1, GR950/16-1, LA2941/4-1, SFB1123/Z2, FR2938/7-1]
- NIHR Cambridge BRC
- IZFK at the University of Wurzburg [Z-6]
- Alexander von Humboldt Foundation
- German Federal Foreign Office
- University of Wuerzburg
- NHSBT [WP11-05, WPA15-02]
- MRC [G1002523, MR/P008801/1] Funding Source: UKRI
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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. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.
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