2026年8月19日，美国耶鲁大学Craig B. Wilen等合作在《细胞》发表研究，系统绘制了小鼠诺如病毒基因组中的RNA结构调控图谱，并通过靶向破坏特定结构元件，成功设计出遗传稳定、可激发保护性免疫且能在二次攻毒时限制病毒复制的减毒病毒株，为RNA结构指导的抗病毒疫苗和药物开发建立了通用框架。

病毒基因组编码调控性RNA结构，这些结构协调病毒复制和基因表达的关键步骤。尽管这些结构日益被认为对病毒功能具有重要调控作用，但在感染背景下对其系统表征，以及其在体内调控病毒适应性和免疫识别中的作用仍较为有限。在此，研究人员利用正交细胞内化学探针技术，对小鼠诺如病毒全基因组的结构化RNA元件进行了系统定位和功能探究，揭示了调控病毒功能的保守基序。对特定结构元件的靶向破坏可降低病毒在细胞培养中的复制水平，在顺式水平上调节翻译，并减少动物感染模型中的病毒RNA载量。这些发现使研究人员能够合理设计出一种遗传稳定、减毒的病毒株，该病毒株可激发保护性免疫，并在二次攻毒时限制病毒复制。

综上，该工作揭示了RNA结构在诺如病毒生物学中的关键作用，并为RNA结构指导的抗病毒疫苗和治疗药物设计建立了一个通用框架。

附：英文原文

Title: RNA structures regulate norovirus life cycle and enable rational attenuation in vivo

Author: Tanja Hann, Arya B. kten, Renata B. Filler, Craig B. Wilen, Anna Marie Pyle

Issue&Volume: 2026-08-19

Abstract: Viral genomes encode regulatory RNA structures that orchestrate key steps of viral replication and gene expression. Although these structures are increasingly recognized as critical regulators of viral function, their systematic characterization in an infection context and roles in regulating viral fitness and immune recognition in vivo remain limited. Here, we systematically map and functionally interrogate structured RNA elements across the murine norovirus genome using orthogonal in-cell chemical probing, revealing conserved motifs that regulate viral function. Targeted disruption of specific structural elements reduces viral replication in cell culture, modulates translation in cis, and decreases viral RNA levels in animal infection models. These findings enabled the rational design of a genetically stable, attenuated virus that elicits protective immunity and limits viral replication upon secondary challenge. Together, this work uncovers essential roles for RNA structure in norovirus biology and establishes a generalizable framework for RNA structure-guided design of antiviral vaccines and therapeutics.

DOI: 10.1016/j.cell.2026.07.051

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00920-7