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Integrative functional genomics decodes herpes simplex virus 1.
Whisnant, Adam W Jürges, Christopher S Hennig, Thomas Wyler, Emanuel Prusty, Bhupesh Rutkowski, Andrzej J L'hernault, Anne Djakovic, Lara Göbel, Margarete Döring, Kristina
Whisnant, Adam W
Jürges, Christopher S
Hennig, Thomas
Wyler, Emanuel
Prusty, Bhupesh
Rutkowski, Andrzej J
L'hernault, Anne
Djakovic, Lara
Göbel, Margarete
Döring, Kristina
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2020-04-27
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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.
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Nat Commun. 2020 Apr 27;11(1):2038. doi: 10.1038/s41467-020-15992-5.
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en
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2041-1723
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Attribution 4.0 International