Cryo-electron microscopy reconstructions of two types of wild rabbit hemorrhagic disease viruses characterized the structural features of Lagovirus
Cryo-electron microscopy reconstructions of two types of wild rabbit hemorrhagic disease viruses characterized the structural features of Lagovirus
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DOI：
10.1007/s13238-010-0007-0
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发表时间：
2010-01-01
期刊：
影响因子：
21.1
通讯作者：
Sun, Fei
中科院分区：
文献类型：
--
作者：
Hu, Zhongjun;Tian, Xiaojuan;Sun, Fei
1984年，中国描述了兔出血性疾病，可能在感染后两到三天内引起肝脏的出血性坏死。病因学剂，兔出血病毒（RHDV）属于乳糜片菌家族中的Lagovirus属。与其他彩色病毒（例如RNV和SMSV）相比，Lagovirus成员的结构没有很好地表征。在本报告中，分别通过冷冻电子显微镜在11 Angstrom和17 Angstrom中重建了两种类型的野生RHDV颗粒的结构，即完整的病毒体和核心粒子（CLP）。这是第一次提供了CLP的野生腔室的3D结构，并且完整的RHDV病毒体的3D结构是Lagovirus中最高的分辨率结构。完整的病毒体和CLP结构的比较清楚地表明，CLP是由完整的病毒体和突出解离的。与重组诺如病毒和圣米格尔海狮病毒的晶体结构相反，RHDV Virion的胶囊表现出独特的结构特征和组装模式。 P1和P2子域在AB帽蛋白酶体内都有相互作用，而只有P2子域在CC capsomer内部具有相互作用。 RHDV胶囊的伪原子模型是通过同源模型和密度图拟合构建的，与SMSV相比，RHDV VP60 P结构域相对于其S域的旋转。总的来说，我们对RHDV的冷冻电子显微镜研究提供了对Lagovirus结构的深入了解，这对于功能分析和将来更好的疫苗开发至关重要。
Rabbit hemorrhagic disease was described in China in 1984 and can cause hemorrhagic necrosis of the liver within two or three days after infection. The etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the Caliciviridae family. Compared to other calicivirus, such as rNV and SMSV, the structure of Lagovirus members is not well characterized. In this report, structures of two types of wild RHDV particles, the intact virion and the core-like particle (CLP), were reconstructed by cryo-electron microscopy at 11 angstrom and 17 angstrom, respectively. This is the first time the 3D structure of wild caliciviruses CLP has been provided, and the 3D structure of intact RHDV virion is the highest resolution structure in Lagovirus. Comparison of the intact virion and CLP structures clearly indicated that CLP was produced from the intact virion with the protrusion dissociated. In contrast with the crystal structures of recombinant Norovirus and San Miguel sea lion virus, the capsomers of RHDV virion exhibited unique structural features and assembly modes. Both P1 and P2 subdomains have interactions inside the AB capsomer, while only P2 subdomains have interaction inside CC capsomer. The pseudo atomic models of RHDV capsomers were constructed by homology modeling and density map fitting, and the rotation of RHDV VP60 P domain with respect to its S domain, compared with SMSV, was observed. Collectively, our cryo-electron microscopic studies of RHDV provide close insight into the structure of Lagovirus, which is important for functional analysis and better vaccine development in the future.