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 Zimmer

Markus 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

66 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",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

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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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