Integrative functional genomics decodes herpes simplex virus 1

Adam W Whisnant; Christopher S Jürges; Thomas Hennig; Emanuel Wyler; Bhupesh Prusty; Andrzej J Rutkowski; Anne L'hernault; Lara Djakovic; Margarete Göbel; Kristina Döring; Jennifer Menegatti; Robin Antrobus; Nicholas J Matheson; Florian W H Künzig; Guido Mastrobuoni; Chris Bielow; Stefan Kempa; Chunguang Liang; Thomas Dandekar; Ralf Zimmer; Markus Landthaler; Friedrich Grässer; Paul J Lehner; Caroline C Friedel; Florian Erhard; Lars Dölken

doi:10.1038/s41467-020-15992-5

Integrative functional genomics decodes herpes simplex virus 1

Adam W Whisnant, Christopher S Jürges, Thomas Hennig, Emanuel Wyler, Bhupesh Prusty, Andrzej J Rutkowski, Anne L'hernault, Lara Djakovic, Margarete Göbel, Kristina Döring, Jennifer Menegatti, Robin Antrobus, Nicholas J Matheson, Florian W H Künzig, Guido Mastrobuoni, Chris Bielow, Stefan Kempa, Chunguang Liang, Thomas Dandekar, Ralf ZimmerMarkus Landthaler, Friedrich Grässer, Paul J Lehner, Caroline C Friedel, Florian Erhard (Corresponding Author), Lars Dölken (Corresponding Author)

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

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.

Original language	English
Article number	2038
Pages (from-to)	1-14
Number of pages	14
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15992-5
Publication status	Published - 27 Apr 2020
Externally published	Yes

Keywords*

Animals
Biological Products/pharmacology
Chlorocebus aethiops
Computational Biology
Cricetinae
Fibroblasts/metabolism
Gene Expression Regulation, Viral/drug effects
Genes, Viral
Genome, Viral
Genomics
Herpesvirus 1, Human/drug effects
Humans
Open Reading Frames
Protein Domains
Protein Isoforms
Ribosomes/metabolism
Transcriptome
Vero Cells

Field of Science*

1.6 Biological sciences
3.1 Basic medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1038/s41467-020-15992-5

Cite this

Whisnant, A. W., Jürges, C. S., Hennig, T., Wyler, E., Prusty, B., Rutkowski, A. J., L'hernault, A., Djakovic, L., Göbel, M., Döring, K., Menegatti, J., Antrobus, R., Matheson, N. J., Künzig, F. W. H., Mastrobuoni, G., Bielow, C., Kempa, S., Liang, C., Dandekar, T., ... Dölken, L. (2020). Integrative functional genomics decodes herpes simplex virus 1. Nature Communications, 11(1), 1-14. Article 2038. https://doi.org/10.1038/s41467-020-15992-5

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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.",

keywords = "Animals, Biological Products/pharmacology, Chlorocebus aethiops, Computational Biology, Cricetinae, Fibroblasts/metabolism, Gene Expression Regulation, Viral/drug effects, Genes, Viral, Genome, Viral, Genomics, Herpesvirus 1, Human/drug effects, Humans, Open Reading Frames, Protein Domains, Protein Isoforms, Ribosomes/metabolism, Transcriptome, Vero Cells",

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year = "2020",

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doi = "10.1038/s41467-020-15992-5",

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Whisnant, AW, Jürges, CS, Hennig, T, Wyler, E, Prusty, B, Rutkowski, AJ, L'hernault, A, Djakovic, L, Göbel, M, Döring, K, Menegatti, J, Antrobus, R, Matheson, NJ, Künzig, FWH, Mastrobuoni, G, Bielow, C, Kempa, S, Liang, C, Dandekar, T, Zimmer, R, Landthaler, M, Grässer, F, Lehner, PJ, Friedel, CC, Erhard, F & Dölken, L 2020, 'Integrative functional genomics decodes herpes simplex virus 1', Nature Communications, vol. 11, no. 1, 2038, pp. 1-14. https://doi.org/10.1038/s41467-020-15992-5

TY - JOUR

T1 - Integrative functional genomics decodes herpes simplex virus 1

AU - Whisnant, Adam W

AU - Jürges, Christopher S

AU - Hennig, Thomas

AU - Wyler, Emanuel

AU - Prusty, Bhupesh

AU - Rutkowski, Andrzej J

AU - L'hernault, Anne

AU - Djakovic, Lara

AU - Göbel, Margarete

AU - Döring, Kristina

AU - Menegatti, Jennifer

AU - Antrobus, Robin

AU - Matheson, Nicholas J

AU - Künzig, Florian W H

AU - Mastrobuoni, Guido

AU - Bielow, Chris

AU - Kempa, Stefan

AU - Liang, Chunguang

AU - Dandekar, Thomas

AU - Zimmer, Ralf

AU - Landthaler, Markus

AU - Grässer, Friedrich

AU - Lehner, Paul J

AU - Friedel, Caroline C

AU - Erhard, Florian

AU - Dölken, Lars

PY - 2020/4/27

Y1 - 2020/4/27

N2 - 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.

AB - 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.

KW - Animals

KW - Biological Products/pharmacology

KW - Chlorocebus aethiops

KW - Computational Biology

KW - Cricetinae

KW - Fibroblasts/metabolism

KW - Gene Expression Regulation, Viral/drug effects

KW - Genes, Viral

KW - Genome, Viral

KW - Genomics

KW - Herpesvirus 1, Human/drug effects

KW - Humans

KW - Open Reading Frames

KW - Protein Domains

KW - Protein Isoforms

KW - Ribosomes/metabolism

KW - Transcriptome

KW - Vero Cells

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Integrative functional genomics decodes herpes simplex virus 1

Abstract

Keywords*

Field of Science*

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