Integrative functional genomics decodes herpes simplex virus 1


  • 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


  • Nature Communications


  • Nat Commun 11 (1): 2038


  • 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.