Integrative functional genomics decodes herpes simplex virus 1

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Item Type:

Article

Title:

Integrative functional genomics decodes herpes simplex virus 1

Creators Name:

Whisnant, A.W. and Jürges, C.S. and Hennig, T. and Wyler, E. and Prusty, B. and Rutkowski, A.J. and L'hernault, A. and Djakovic, L. and Göbel, M. and Döring, K. and Menegatti, J. and Antrobus, R. and Matheson, N.J. and Künzig, F.W.H. and Mastrobuoni, G. and Bielow, C. and Kempa, S. and Liang, C. and Dandekar, T. and Zimmer, R. and Landthaler, M. and Grässer, F. and Lehner, P.J. and Friedel, C.C. and Erhard, F. and Dölken, L.

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.

Keywords:

Biological Products, Computational Biology, Fibroblasts, Viral Gene Expression Regulation, Viral Genes, Viral Genome, Genomics, Human Herpesvirus 1, Open Reading Frames, Protein Domains, Protein Isoforms, Ribosomes, Transcriptome, Vero Cells, Animals, Chlorocebus aethiops, Cricetinae

Source:

Nature Communications

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Volume:

Number:

Page Range:

2038

Date:

27 April 2020