不同状态禽呼肠孤病毒的冷冻电镜结构研究
刘京路#, 高 立#, 王有望, 祁小乐, 张雪利，包珂岩, 高玉龙*, 王笑梅*, 朱 平*
(1. 中国科学院生物物理研究所 表观遗传调控与干预重点实验室，北京 100101; 2. 中国农业科学院哈尔滨兽医研究所 动物疫病防控全国重点实验室 禽免疫抑制病创新团队，黑龙江 哈尔滨 150069; 3. 西南民族大学 畜牧兽医学院，四川 成都 610041 ; 4. 中国科学院大学，北京 100049)
摘 要 禽呼肠孤病毒（Avian reovirus，ARV）是一种双链RNA 病毒，对家禽养殖业构成严重威胁。本文利用冷冻电镜技术解析了ARV病毒的完整病毒颗粒（virion）以及处于转录状态的病毒核心颗粒（T-core）的高分辨率三维结构。对比分析表明，ARV病毒virion和T-core颗粒的塔状突起蛋白λC存在明显结构差异，显示其在病毒转录过程中的重要作用。在病毒转录态核心颗粒中，作者发现σA蛋白与双链RNA存在较强结合，并确认了起关键作用的氨基酸残基。同时，分析了ARV病毒内部转录酶RdRP以及基因组三维结构，获得了处于转录过程中ARV病毒核心颗粒内部基因组的三维分布。
关键词 禽呼肠孤病毒；冷冻电镜；塔状突起；RdRP；双链RNA
中图分类号： Q71；S831.7；S852.62；Q336 文献标识码：A Doi:10.3969/j.issn.1000-6281.2025.01.002
Cryo-EM structural analysis of avian reovirus in different states
LIU Jinglu#, GAO Li2#, WANG Youwang, QI Xiaole, ZHANG Xueli，BAO Keyan, GAO Yulong*, WANG Xiaomei*, ZHU Ping*
(1. Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics of the Chinese Academy of Sciences, Beijing 100101；2. State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin Heilongjiang 150069；3. College of Animal Science and Veterinary Medicine, Southwest Minzu University, Chengdu Sichuan 610041；4. University of Chinese Academy of Sciences, Beijing 100049, China)
Abstract Avian reovirus (ARV) is a double-stranded RNA virus that poses a serious threat to the poultry industry. In this study, we employed cryo-electron microscopy (cryo-EM) to resolve the three-dimensional structures of both the virion and the transcribing core particle (T-core) of ARV. Comparative analysis revealed significant difference in the structures of turrent protein λC in the virion and T-core particles, suggesting that λC plays a key role in the transcription process of ARV. Additionally, the σA protein in the T-core particle exhibits strong binding to the double-stranded RNA, and the key amino acid residues involved in this binding were identified. Furthermore, we analyzed the internal structures of viral RNA-dependent RNA polymerase (RdRP), which revealed the three-dimensional organization and distribution of the RNA genome within the transcribing ARV core particle.
Keywords Avian reovirus; Cryo-EM; turret; RdRP; double-stranded-RNA
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