戊型肝炎病毒基因1型和基因4型中和表位区域分子差异研究The Molecular Differences between Genotype 1 and Genotype 4 of HEV in Their Neutralization Region
郭清顺;葛胜祥;熊君辉;闫强;李少伟;顾颖;徐平东;史维国;张军;夏宁邵;
摘要(Abstract):
戊型肝炎病毒(HEV)根据易感宿主的差别可以分为两大类:一类只分离自人的H(Human)类,包括HEV-1和HEV-2;一类为人畜共患的Z(Zoonosis)类,包括HEV-3和HEV-4。本研究通过比较这两类HEV的ORF2aa368606区段,发现存在4个类保守的差异位点,均位于HEV的主要中和表位区域aa459606区段,发现存在4个类保守的差异位点,均位于HEV的主要中和表位区域aa459606,分别是aa483、aa492、aa497和aa599;对这四个位点进行定点替换突变,以一组能够捕获HEV-1和/或HEV-4的单克隆抗体比较各种突变体的免疫反应性,结果表明仅aa497的差异造成了这两类HEV中和表位构象的部分差异,提示aa497及其相关的病毒表面结构差异在H类和Z类HEV宿主选择中可能扮演重要角色。
关键词(KeyWords): 戊型肝炎病毒;宿主差异;中和表位
基金项目(Foundation): 863计划(2005DFA30820);; 国家自然科学基金(30500092);; 国家自然科学基金(30600106);; 福建省科技重大专项(2004YZ01-1)
作者(Authors): 郭清顺;葛胜祥;熊君辉;闫强;李少伟;顾颖;徐平东;史维国;张军;夏宁邵;
参考文献(References):
- [1]Emerson S U,Purcell R H.Hepatitis E virus[J].RevMed Virol,2003,13(3):145-154.
- [2]Balayan M S,Andjaparidze A G,Savinskaya S S,et al.Evidence for a virus in non-A,non-B hepatitis transmit-ted via the fecal-oral route[J].Intervirology,1983,20(1):23-31.
- [3]Bradley D W,Krawczynski K,Cook E H,et al.Enteri-cally transmitted non-A,non-B hepatitis:serial passageof disease in cynomolgus macaques and tamarins and re-covery of disease-associated 27-to 34-nm virus-like parti-cles[J].Proc Natl Acad Sci USA,1987,84(17):6277-6281.
- [4]Matsuda H,Okada K,Takahashi K,et al.Severe hepa-titis E virus infection after ingestion of uncooked liverfrom a wild boar[J].J Infect Dis,2003,188(6):944.
- [5]Masuda J I,Yano K,Tamada Y,et al.Acute hepatitisE of a man who consumed wild boar meat prior to the on-set of illness in Nagasaki,Japan[J].Hepatol Res,2005,31(3):178-183.
- [6]Tei S,Kitajima N,Takahashi K,et al.Zoonotic trans-mission of hepatitis E virus from deer to human beings[J].Lancet,2003,362(9381):371-373.
- [7]Zheng Y,Ge S,Zhang J,et al.Swine as a principal res-ervoir of hepatitis E virus that infects humans in easternChina[J].J Infect Dis,2006,193(12):1643-1649.
- [8]Li S W,Zhang J,He Z Q,et al.Mutational analysis ofessential interactions involved in the assembly of hepatitisE virus capsid[J].J Biol Chem,2005,280(5):3400-3406.
- [9]何水珍,郑子峥,吴婷,等.戊型肝炎病毒细胞吸附模型的建立及病毒吸附区域初步研究[J].病毒学报,2006,22(6):426-430.
- [10]何志强,张军,李少伟,等.颗粒化重组戊型肝炎病毒衣壳蛋白及其抗原性与免疫原性[J].生物工程学报,2004,20(2):262-268.
- [11]张军,李益民,李少伟,等.大肠杆菌重组颗粒性戊型肝炎疫苗对恒河猴的免疫保护[J].病毒学报,2004,20(1):1-6.