在科技部、國家自然科學(xué)基金委員會和中科院的資助下，中科院生物物理所孫飛研究組與其合作者在兔出血癥病毒結(jié)構(gòu)及其表位抗原研究中取得重大突破,，該成果近日在線發(fā)表于國際病原學(xué)雜志《公共科學(xué)圖書館—病原體》（PLOS Pathogens）,。
兔出血癥（RHD）是一種急性,、致死傳染病,，家兔在感染后48～72小時死亡。1984年,，中國首次報道了兔出血癥的暴發(fā),，隨后在歐洲、美洲等地區(qū)逐漸流行,。該病的病原體兔出血癥病毒（RHDV）隸屬杯狀病毒科兔病毒屬,。相比杯狀病毒科其他病毒屬，有關(guān)兔病毒屬病毒的高分辨率結(jié)構(gòu)研究尚屬空白,。
孫飛等通過對RHDV衣殼蛋白的結(jié)構(gòu)進行分析以及不同病毒株的序列比對，設(shè)計出一段多肽,，通過受體結(jié)合實驗證明了該多肽可以和兔的組織細胞結(jié)合,，且中和實驗結(jié)果表明該多肽能有效刺激細胞產(chǎn)生抗體,，利用該多肽制備的疫苗可以有效防御RHDV的感染。
該項研究對于研制新型的兔出血癥疫苗具有重要作用,，同時也將促進基于兔出血癥病毒的新型抗原呈遞載體的開發(fā),。此外，本項研究綜合應(yīng)用了低溫電鏡三維重構(gòu)技術(shù),、X射線晶體學(xué)和分子動力學(xué)模擬技術(shù),，最終獲得了RHDV的高分辨率準(zhǔn)原子模型，為綜合運用多種技術(shù)手段解析生物超大分子復(fù)合體的高分辨率結(jié)構(gòu)樹立了新范例,。（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.
