%0 Journal Article %1 Whisnant603654 %A Whisnant, Adam W. %A Jürges, Christopher S. %A Hennig, Thomas %A Wyler, Emanuel %A Prusty, Bhupesh %A Rutkowski, Andrzej J %A L’hernault, Anne %A Göbel, Margarete %A Döring, Kristina %A Menegatti, Jennifer %A Antrobus, Robin %A Matheson, Nicholas J. %A Künzig, Florian W.H. %A Mastrobuoni, Guido %A Bielow, Chris %A Kempa, Stefan %A Chunguang, Liang %A Dandekar, Thomas %A Zimmer, Ralf %A Landthaler, Markus %A Grässer, Friedrich %A Lehner, Paul J. %A Friedel, Caroline C. %A Erhard, Florian %A Dölken, Lars %D 2019 %I Cold Spring Harbor Laboratory %J bioRxiv %K myown %R 10.1101/603654 %T Integrative functional genomics decodes herpes simplex virus 1 %U https://www.biorxiv.org/content/early/2019/04/09/603654 %X 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.

@article{Whisnant603654, 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.}, added-at = {2019-10-23T16:38:55.000+0200}, author = {Whisnant, Adam W. and J{\"u}rges, Christopher S. and Hennig, Thomas and Wyler, Emanuel and Prusty, Bhupesh and Rutkowski, Andrzej J and L{\textquoteright}hernault, Anne and G{\"o}bel, Margarete and D{\"o}ring, Kristina and Menegatti, Jennifer and Antrobus, Robin and Matheson, Nicholas J. and K{\"u}nzig, Florian W.H. and Mastrobuoni, Guido and Bielow, Chris and Kempa, Stefan and Chunguang, Liang and Dandekar, Thomas and Zimmer, Ralf and Landthaler, Markus and Gr{\"a}sser, Friedrich and Lehner, Paul J. and Friedel, Caroline C. and Erhard, Florian and D{\"o}lken, Lars}, biburl = {https://www.bibsonomy.org/bibtex/2c33b186fd8c6613ce55715cd4a420537/cusysmed}, day = 09, doi = {10.1101/603654}, elocation-id = {603654}, eprint = {https://www.biorxiv.org/content/early/2019/04/09/603654.full.pdf}, interhash = {6158baa79a764d0aec3161c1d98dce8e}, intrahash = {c33b186fd8c6613ce55715cd4a420537}, journal = {bioRxiv}, keywords = {myown}, month = {April}, publisher = {Cold Spring Harbor Laboratory}, timestamp = {2019-10-24T14:48:47.000+0200}, title = {Integrative functional genomics decodes herpes simplex virus 1}, url = {https://www.biorxiv.org/content/early/2019/04/09/603654}, year = 2019 }