Integrative functional genomics decodes herpes simplex virus 1.
Adam W WhisnantChristopher S JürgesThomas HennigEmanuel WylerBhupesh Kumar PrustyAndrzej J RutkowskiAnne L'hernaultLara DjakovicMargarete GöbelKristina DöringJennifer MenegattiRobin AntrobusNicholas J MathesonFlorian W H KünzigGuido MastrobuoniChris BielowStefan KempaChunguang LiangThomas DandekarRalf ZimmerMarkus LandthalerFriedrich GrässerPaul J LehnerCaroline C FriedelFlorian ErhardLars DölkenPublished in: Nature communications (2020)
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.
Keyphrases
- herpes simplex virus
- genome wide
- sars cov
- single cell
- rna seq
- electronic health record
- copy number
- dna methylation
- big data
- minimally invasive
- single molecule
- gene expression
- working memory
- genome wide association study
- genome wide identification
- transcription factor
- machine learning
- data analysis
- small molecule
- protein protein
- deep learning
- network analysis
- drug administration