在科技部、国家自然科学基金委员会和中科院的资助下，中科院生物物理所孙飞研究组与其合作者在兔出血症病毒结构及其表位抗原研究中取得重大突破，该成果近日在线发表于国际病原学杂志《公共科学图书馆—病原体》（PLOS Pathogens）。
兔出血症（RHD）是一种急性、致死传染病，家兔在感染后48～72小时死亡。1984年，中国首次报道了兔出血症的暴发，随后在欧洲、美洲等地区逐渐流行。该病的病原体兔出血症病毒（RHDV）隶属杯状病毒科兔病毒属。相比杯状病毒科其他病毒属，有关兔病毒属病毒的高分辨率结构研究尚属空白。
孙飞等通过对RHDV衣壳蛋白的结构进行分析以及不同病毒株的序列比对，设计出一段多肽，通过受体结合实验证明了该多肽可以和兔的组织细胞结合，且中和实验结果表明该多肽能有效刺激细胞产生抗体，利用该多肽制备的疫苗可以有效防御RHDV的感染。
该项研究对于研制新型的兔出血症疫苗具有重要作用，同时也将促进基于兔出血症病毒的新型抗原呈递载体的开发。此外，本项研究综合应用了低温电镜三维重构技术、X射线晶体学和分子动力学模拟技术，最终获得了RHDV的高分辨率准原子模型，为综合运用多种技术手段解析生物超大分子复合体的高分辨率结构树立了新范例。（生物谷Bioon.com）
doi:10.1371/journal.ppat.1003132
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Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography
Wang X, Xu F, Liu J, Gao B, Liu Y, et al.
Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be determined. Here, we report a cryo-electron microscopic (cryoEM) reconstruction of wild-type RHDV at 6.5 ? resolution and the crystal structures of the shell (S) and protruding (P) domains of its major capsid protein, VP60, each at 2.0 ? resolution. From these data we built a complete atomic model of the RHDV capsid. VP60 has a conserved S domain and a specific P2 sub-domain that differs from those found in other caliciviruses. As seen in the shell portion of the RHDV cryoEM map, which was resolved to ~5.5 ?, the N-terminal arm domain of VP60 folds back onto its cognate S domain. Sequence alignments of VP60 from six groups of RHDV isolates revealed seven regions of high variation that could be mapped onto the surface of the P2 sub-domain and suggested three putative pockets might be responsible for binding to histo-blood group antigens. A flexible loop in one of these regions was shown to interact with rabbit tissue cells and contains an important epitope for anti-RHDV antibody production. Our study provides a reliable, pseudo-atomic model of a Lagovirus and suggests a new candidate for an efficient vaccine that can be used to protect rabbits from RHDV infection.
