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作 者:刘刚[1] 梁争论[1] 蔡孟深[1] 孙涛[1] 庄辉[1] 陶其敏[1] 郭建平[1]
机构地区:[1]北京医科大学药学院有机化学研究室,北京医科大学公共卫生学院流行病学研究室,北京军事医学科学院基础医学研究所,北京医科大学人民医院肝病研究所
出 处:《药学学报》1996年第5期358-363,共6页Acta Pharmaceutica Sinica
基 金:卫生部"八五"招标项目
摘 要:丙型肝炎病毒(HCV)基因组有显著的异源性和高度的可变性。其中E2HV(高变区)认为是宿主识别HCV,并且产生免疫压力的靶目标之一。文中设计并合成了三段多肽抗原P2,P9和P10。抗原性及免疫原性研究结果表明:(1)HCV宿主体内存在抗-E2HV抗体,但这种抗体是非中和性的,或者是抗体滴度太低。不足以中和HC病毒抗原;(2)同一基因型的HCV抗-E2HV抗体有某种共同的结构特点,从而使某一HCV病毒株E2HV抗原能够与其它病毒株抗-E2HV抗体反应,大约有30%的代表性;(3)丙型肝炎病毒E2HV区里碳端398~412多肽片段可以引起动物免疫应答。HCV has characteristics of rapid variablity.The amino terminus of E2/NS1 ofHCV(amino acids sequence 384~414),which is hypervariable with respect to both nucleotide andamino acid sequence,has been termed the E2 HV domain or HVR1. The E2 HV domain appears to bearapidly evolving region of the HCV genolnes which may contain linear neutralizing epitopes and theE2 HV are under immune selection, For further studies of the immunogenicity on E2 HV of HCV,weselected three peptide fragments from the full length of E2 HV region sequence and synthesized themwith SPPS method. The amino acid sequences are shown as following:P2:VDGDTHVT-GGAQAKTTNR(381~398);P9:STHVTGAVQGHSIRGTTSLFTSGPAQKIQ(384~412);P10:RTYTSGGTAGHTTSGITSLFSPGASQKIQ(384~412), From the results of ELISA and anti-peptideAbs of rabbit sera,we conclude that there are anti-E2 HV Abs in immune host but they could notneutralize HCV,so these Abs were not reactive with all E2 HV epitopes that resulted in immuneselection of escape mutants;the anti-E2 HV Abs,probably from the same genotype,contained somecommon structure in which E2 HV epitopes react with other anti-E2 HV Abs at 30%;the C-terminusof E2 HV region(398~412)caused the immune response to rabbits.
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