Integrative functional genomics decodes herpes simplex virus 1
Autor/innen
- A.W. Whisnant
- C.S. Jürges
- T. Hennig
- E. Wyler
- B. Prusty
- A.J. Rutkowski
- A. L'hernault
- L. Djakovic
- M. Göbel
- K. Döring
- J. Menegatti
- R. Antrobus
- N.J. Matheson
- F.W.H. Künzig
- G. Mastrobuoni
- C. Bielow
- S. Kempa
- C. Liang
- T. Dandekar
- R. Zimmer
- M. Landthaler
- F. Grässer
- P.J. Lehner
- C.C. Friedel
- F. Erhard
- L. Dölken
Journal
- Nature Communications
Quellenangabe
- Nat Commun 11 (1): 2038
Zusammenfassung
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.