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 () and Lars Dölken ()
Additional contact information
Adam W. Whisnant: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Christopher S. Jürges: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Thomas Hennig: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Emanuel Wyler: Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine
Bhupesh Prusty: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Andrzej J. Rutkowski: Department of Medicine, University of Cambridge, Box 157, Addenbrookes Hospital
Anne L’hernault: Department of Medicine, University of Cambridge, Box 157, Addenbrookes Hospital
Lara Djakovic: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Margarete Göbel: Julius-Maximilians-University Würzburg
Kristina Döring: Julius-Maximilians-University Würzburg
Jennifer Menegatti: Saarland University Medical School
Robin Antrobus: University of Cambridge
Nicholas J. Matheson: University of Cambridge
Florian W. H. Künzig: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Guido Mastrobuoni: Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine
Chris Bielow: Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine
Stefan Kempa: Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine
Chunguang Liang: Julius-Maximilians-University Würzburg
Thomas Dandekar: Julius-Maximilians-University Würzburg
Ralf Zimmer: Ludwig-Maximilians-Universität München
Markus Landthaler: Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine
Friedrich Grässer: Saarland University Medical School
Paul J. Lehner: University of Cambridge
Caroline C. Friedel: Ludwig-Maximilians-Universität München
Florian Erhard: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7
Lars Dölken: Institute for Virology and Immunobiology, Julius-Maximilians-University Würzburg, Versbacher Straße 7

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15992-5

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