Journal Article

Integrative functional genomics decodes herpes simplex virus 1

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

2020

Overview

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. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 49/39 / 631/114 / 631/326/596/1553 / Animals / Biological Products - pharmacology / Chlorocebus aethiops / Codons / Computational Biology / Computer applications / Cricetinae / Fibroblasts - metabolism / Gene expression / Gene Expression Regulation, Viral - drug effects / Genes, Viral / Genome, Viral / Genomes / Genomics / Herpes simplex / Herpes viruses / Herpesvirus 1, Human - drug effects / Herpesvirus 1, Human - genetics / Humanities and Social Sciences / Humans / Integration / Isoforms / Localization / Loci / multidisciplinary / Nucleotides / Oncolysis / Open Reading Frames / Packaging / Protein Domains / Protein Isoforms / Proteins / Regulators / Ribosomes - metabolism / Science / Science (multidisciplinary) / Structural proteins / Transcription / Transcriptome / Vero Cells / Viruses