利用大规模平行核糖体分析发现泛病毒ORF，这一成果由美国哈佛大学
研究组开发了大量平行核糖体分析（MPRP）来确定数十个设计寡核苷酸的开放阅读框（ORF）。MPRP在679个人类相关病毒基因组中鉴定出4208个未注释的ORF。研究小组发现病毒肽来源于检测到的非规范ORF，这些ORF出现在感染细胞的I类人白细胞抗原上，并且数百个上游ORF可能调节病毒蛋白的翻译起始。病毒ORF在广泛的病毒家族（包括高致病性病毒主题）中的发现，扩大了疫苗靶点的范围，并揭示了潜在的顺式调控序列。
据了解，定义病毒蛋白质组对于理解病毒生命周期和免疫识别至关重要，但对于大多数病毒主题来说，翻译区域的景观仍然未知。
附：英文原文
Title: Pan-viral ORFs discovery using massively parallel ribosome profiling
Author: Shira Weingarten-Gabbay, Matthew R. Bauer, Alexandra C. Stanton, Yingpu Yu, Catherine A. Freije, Nicole L. Welch, Chloe K. Boehm, Susan Klaeger, Eva K. Verzani, Daniel López, Lisa E. Hensley, Karl R. Clauser, Steven A. Carr, Jennifer G. Abelin, Charles M. Rice, Pardis C. Sabeti
Issue&Volume: 2025-06-12
Abstract: 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.
DOI: ado6670
Source: https://www.science.org/doi/10.1126/science.ado6670