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^*, Lars Dölken

^*Corresponding author for this work

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

64 Scopus citations

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
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15992-5
State	Published - 1 Dec 2020
Externally published	Yes

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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), Article 2038. https://doi.org/10.1038/s41467-020-15992-5

@article{2c551fd283b2456597995bd2aaae1a58,

title = "Integrative functional genomics decodes herpes simplex virus 1",

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.",

author = "Whisnant, \{Adam W.\} and J{\"u}rges, \{Christopher S.\} and Thomas Hennig and Emanuel Wyler and Bhupesh Prusty and Rutkowski, \{Andrzej J.\} and Anne L{\textquoteright}hernault and Lara Djakovic and Margarete G{\"o}bel and Kristina D{\"o}ring and Jennifer Menegatti and Robin Antrobus and Matheson, \{Nicholas J.\} and K{\"u}nzig, \{Florian W.H.\} and Guido Mastrobuoni and Chris Bielow and Stefan Kempa and Chunguang Liang and Thomas Dandekar and Ralf Zimmer and Markus Landthaler and Friedrich Gr{\"a}sser and Lehner, \{Paul J.\} and Friedel, \{Caroline C.\} and Florian Erhard and Lars D{\"o}lken",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

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

language = "English",

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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. 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 - 2020/12/1

Y1 - 2020/12/1

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.

UR - https://www.scopus.com/pages/publications/85083956760

U2 - 10.1038/s41467-020-15992-5

DO - 10.1038/s41467-020-15992-5

M3 - Article

C2 - 32341360

AN - SCOPUS:85083956760

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2038

ER -

Integrative functional genomics decodes herpes simplex virus 1

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