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Whisnant, Adam W.; Jürges, Christopher S.; Hennig, Thomas; Wyler, Emanuel; Prusty, Bhupesh; Rutkowski, Andrzej J.; L'hernault, Anne; Djakovic, Lara; Goebel, Margarete; Doering, Kristina; Menegatti, Jennifer; Antrobus, Robin; Matheson, Nicholas J.; Künzig, Florian W. H.; Mastrobuoni, Guido; Bielow, Chris; Kempa, Stefan; Liang, Chunguang; Dandekar, Thomas; Zimmer, Ralf; Landthaler, Markus; Graesser, Friedrich; Lehner, Paul J.; Friedel, Caroline C.; Erhard, Florian and Dölken, Lars (2020): Integrative functional genomics decodes herpes simplex virus 1. In: Nature Communications, Vol. 11, No. 1, 2038 [PDF, 2MB]

Abstract

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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