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Integrative functional genomics decodes herpes simplex virus 1

Item Type:Preprint
Title:Integrative functional genomics decodes herpes simplex virus 1
Creators Name:Whisnant, A.W. and Jürges, C.S. and Hennig, T. and Wyler, E. and Prusty, B. and Rutkowski, A.J. and L’hernault, A. and Göbel, M. and Döring, K. and Menegatti, J. and Antrobus, R. and Matheson, N.J. and Künzig, F.W.H. and Mastrobuoni, G. and Bielow, C. and Kempa, S. and Chunguang, L. and Dandekar, T. and Zimmer, R. and Landthaler, M. and Grässer, F. and Lehner, P.J. and Friedel, C.C. and Erhard, F. and Dölken, L.
Abstract:Since the genome of herpes simplex virus 1 (HSV-1) was first sequenced more than 30 years ago, its predicted 80 genes have been intensively studied. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identified a total of 201 viral transcripts and 284 open reading frames (ORFs) including all known and 46 novel large ORFs. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of novel viral ORFs as well as N-terminal extensions (NTEs) and truncations thereof. We show that key viral regulators and structural proteins possess NTEs, which initiate from non-canonical start codons and govern subcellular protein localization and packaging. We validated a novel non-canonical large spliced ORF in the ICP0 locus and identified a 93 aa ORF overlapping ICP34.5 that is thus also deleted in the FDA-approved oncolytic virus Imlygic. Finally, we extend the current nomenclature to include all novel viral gene products. Taken together, this work provides a valuable resource for future functional studies, vaccine design and oncolytic therapies.
Keywords:Herpes Simplex Virus, Ribosome Profiling, RNA-Seq, 4sU-Seq, Quantitative Proteomics, Transcriptomics, Gene Expression, Nomenclature
Publisher:Cold Spring Harbor Laboratory Press
Article Number:603654
Date:9 April 2019
Official Publication:https://doi.org/10.1101/603654
Related to:
https://edoc.mdc-berlin.de/18895/Final version

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