ArticlebioRxiv : the preprint server for biology2023
Pan-viral ORFs discovery using Massively Parallel Ribosome Profiling.
Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unveiling the complete proteome of viruses is crucial to our understanding of the viral life cycle and interaction with the host. We developed Massively Parallel Ribosome Profiling (MPRP) to experimentally determine open reading frames (ORFs) in 20,170 designed oligonucleotides across 679 human-associated viral genomes. We identified 5,381 ORFs, including 4,208 non-canonical ORFs, and show successful detection of both annotated coding sequences (CDSs) and reported non-canonical ORFs. By examining immunopeptidome datasets of infected cells, we found class I human leukocyte antigen (HLA-I) peptides originating from non-canonical ORFs identified through MPRP. By inspecting ribosome occupancies on the 5'UTR and CDS regions of annotated viral genes, we identified hundreds of upstream ORFs (uORFs) that negatively regulate the synthesis of canonical viral proteins. The unprecedented source of viral ORFs across a wide range of viral families, including highly pathogenic viruses, expands the repertoire of vaccine targets and exposes new cis-regulatory sequences in viral genomes.
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