Back to Search Start Over

Integrative functional genomics decodes herpes simplex virus 1

Authors :
Florian W. H. Künzig
Thomas Hennig
Markus Landthaler
Paul J. Lehner
Stefan Kempa
Chunguang Liang
Caroline C. Friedel
Christopher S. Jürges
Thomas Dandekar
Florian Erhard
Margarete Göbel
Robin Antrobus
Adam W. Whisnant
Emanuel Wyler
Kristina Döring
Lars Dölken
Chris Bielow
Bhupesh K. Prusty
Anne L’Hernault
Ralf Zimmer
Nicholas J Matheson
Friedrich A. Grässer
Jennifer Menegatti
Guido Mastrobuoni
Andrzej J. Rutkowski
Publication Year :
2019
Publisher :
Cold Spring Harbor Laboratory, 2019.

Abstract

SummarySince 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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....f611cb225490ef6d491008256de7d4f5