德国法兰克福歌德大学Ivan Dikic小组的一项最新研究研制了程序性核糖体移框触发翻译应激以促进病毒复制。相关论文于近日发表在《细胞》杂志上。
程序性核糖体移码（PRF）是病毒从紧凑基因组表达多聚蛋白的一种保守策略。尽管PRF传统上被视为一种结构性机制，但在此研究人员表明，它作为一种调控信号发挥作用，重塑宿主翻译以有利于病毒复制。一个最小的SARS-CoV-2 PRF元件足以独立于经典ISR传感器ZAKα激活整合应激反应（ISR）的GCN2分支。这种激活在感染早期作为时间开关关闭宿主翻译，并且是病毒在细胞和人气道类器官中传播所必需的。蛋白质组学和遗传学筛选鉴定出DRG1和IGF2BP3是PRF诱导GCN2激活的关键介导因子。研究人员进一步表明，这一PRF-GCN2轴在人类免疫缺陷病毒（HIV）-1和西尼罗病毒中保守，凸显了其跨RNA病毒的广泛相关性。这些发现揭示了病毒翻译控制的一种精密机制，凸显PRF作为一种增强病毒复制的应激诱导模块。
附：英文原文
Title: Programmed ribosomal frameshifting triggers translational stress to promote viral replication
Author: Audrey Xavier, Melinda Kolling, Ashley M. Bourke, Thorsten Mosler, Cristian Prieto-Garcia, Emil Karaulanov, Michaela Reissland, Michel Tassetto, Damian Kim, Katleen Klaassen, Katharina Grikscheit, Emma Torbica, Verena Dederer, Jonas Busam, Rubina Kazi, Ruth Olmer, Srinivas Reddy Pallerla, Sebastian Mathea, Markus E. Diefenbacher, Kathi Zarnack, Denisa Bojkova, Marek Widera, Ranen Aviner, Raul Andino, Sandra Ciesek, Ivan Dikic
Issue&Volume:
Abstract: Programmed ribosomal frameshifting (PRF) is a conserved viral strategy for expressing polyproteins from compact genomes. Although PRF is traditionally viewed as a structural mechanism, here we show that it functions as a regulatory signal that rewires host translation in favor of viral replication. A minimal SARS-CoV-2 PRF element is sufficient to activate the GCN2 arm of the integrated stress response (ISR) independently of the canonical ISR sensor ZAKα. This activation serves as a temporal switch during early infection to shut off host translation and is required for viral propagation in cells and human airway organoids. Proteomic and genetic screens identify DRG1 and IGF2BP3 as key mediators of PRF-induced GCN2 activation. We further show that this PRF-GCN2 axis is conserved in human immunodeficiency virus (HIV)-1 and West Nile virus, highlighting its broad relevance across RNA viruses. These findings reveal a sophisticated mechanism of viral translational control, highlighting PRF as a stress-inducing module that enhances viral replication.
DOI: 10.1016/j.cell.2026.08.031
Source: https://www.cell.com/cell/abstract/S0092-8674(26)01004-4