文献类型： 外文期刊

作者： Ruan, Zhiyang ¹ ; Shao, Qianqian ¹ ; Song, Yanhua ³ ; Hu, Bo ³ ; Fan, Zhiyu ³ ; Wei, Houjun ³ ; Liu, Yunshu ¹ ; Wang, Fang ³ ; Fang, Qianglin ¹ ;

作者机构： 1.Sun Yat sen Univ, Sch Publ Hlth Shenzhen, Shenzhen Campus, Shenzhen, Guangdong, Peoples R China

2.Sun Yat sen Univ, Shenzhen Key Lab Pathogen Microbes & Biosafety, Shenzhen Campus, Shenzhen, Guangdong, Peoples R China

3.Jiangsu Acad Agr Sci, Inst Vet Med, Natl Ctr Engn Res Vet Bioprod, Key Lab Vet Biol Engn & Technol,Minist Agr, Nanjing, Peoples R China

4.GuoTai Taizhou Ctr Technol Innovat Vet Biol, Taizhou, Peoples R China

关键词： rabbit hemorrhagic disease virus (RHDV); cryo-EM; capsid; virus-like particles (VLP)

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：3.8； 五年影响因子：3.9 ）

ISSN： 0022-538X

年卷期： 2024 年 98 卷 11 期

页码：

收录情况： SCI

摘要： Rabbit hemorrhagic disease virus (RHDV) poses a significant threat to rabbits, causing substantial economic losses in rabbit farming. The virus also endangers wild populations of rabbit species and the predatory animals that rely on rabbits as a food source, thereby disturbing the ecological balance. However, the structural understanding of RHDV has been limited due to the lack of high-resolution structures. Here, we present the first high-resolution cryo-EM structures of the mature virion and virus-like particles (VLPs) derived from both full-length and N-terminal arm (NTA)-truncated VP60. These structures reveal intricate structural details of the icosahedral capsid and crucial NTA-mediated interactions essential for capsid assembly. In addition, dramatic conformational differences are unexpectedly observed between the mature virion and VLP. The protruding spikes of the A-B dimers adopt a "raised" state in the mature virion and a "resting" state in the VLP. These findings enhance our understanding of the structure, assembly, and conformational dynamics of the RHDV capsid, laying the essential groundwork for further virological research and therapeutic advancements.IMPORTANCERHDV is a pathogen with significant economic and ecological impact. By presenting the first high-resolution cryo-EM structures of RHDV, we have uncovered detailed interactions among neighboring VP60 subunits of the icosahedral capsid. The NTA of VP60 is uniquely clustered around the threefold axis of the capsid, probably play a critical role in dragging the six VP60 dimers around the threefold axis during capsid assembly. Additionally, we observed dramatic conformational differences between the mature virion and VLPs. VLPs are commonly used for vaccine development, under the assumption that their structure closely resembles that of the mature virion. Our findings significantly advance the understanding of the RHDV capsid structure, which may be used for developing potential therapeutic strategies against RHDV. RHDV is a pathogen with significant economic and ecological impact. By presenting the first high-resolution cryo-EM structures of RHDV, we have uncovered detailed interactions among neighboring VP60 subunits of the icosahedral capsid. The NTA of VP60 is uniquely clustered around the threefold axis of the capsid, probably play a critical role in dragging the six VP60 dimers around the threefold axis during capsid assembly. Additionally, we observed dramatic conformational differences between the mature virion and VLPs. VLPs are commonly used for vaccine development, under the assumption that their structure closely resembles that of the mature virion. Our findings significantly advance the understanding of the RHDV capsid structure, which may be used for developing potential therapeutic strategies against RHDV.