Pan-viral ORFs discovery using massively parallel ribosome profiling

• 成果类型: Article
• 署名作者: Weingarten-Gabbay, Shira; Bauer, Matthew R.; Stanton, Alexandra C.; Yu, Yingpu; Freije, Catherine A.; Welch, Nicole L.; Boehm, Chloe K.; Klaeger, Susan; Verzani, Eva K.; Lopez, Daniel; Hensley, Lisa E.; Clauser, Karl R.; Carr, Steven A.; Abelin, Jennifer G.; Rice, Charles M.; Sabeti, Pardis C.
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Rockefeller University; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Instituto de Salud Carlos III; Centro Nacional de Microbiologia (CNM); United States Department of Agriculture (USDA); Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard Medical School; Harvard University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8280
• DOI: 10.1126/science.ado6670
• 发表日期: 2025-06-12
• 页码: 1218-1224
• 关键词: hepatitis-c virus; translation initiation; cryptic epitopes; in-vivo; reveals; replication; expression; peptides; protein; gene

摘要

Defining viral proteomes is crucial to understanding viral life cycles and immune recognition but the landscape of translated regions remains unknown for most viruses. We have developed massively parallel ribosome profiling (MPRP) to determine open reading frames (ORFs) across tens of thousands of designed oligonucleotides. MPRP identified 4208 unannotated ORFs in 679 human-associated viral genomes. We found viral peptides originating from detected noncanonical ORFs presented on class-I human leukocyte antigen in infected cells and hundreds of upstream ORFs that likely modulate translation initiation of viral proteins. The discovery of viral ORFs across a wide range of viral families-including highly pathogenic viruses-expands the repertoire of vaccine targets and reveals potential cis-regulatory sequences.