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基于Ii分子的HCV-NS3 Th1表位基因疫苗的设计及功能研究

发布时间:2018-12-16 11:03
【摘要】:丙型病毒性肝炎是严重危害人类健康的传染病。全球丙肝病毒(HCV)的感染人数约为一亿七千万,占世界人口总数的1—3%。在感染的人群中,约8O%转为慢性,20%发展为肝硬化和肝细胞癌;我国的HCV感染者占人口总数的3.2%,估计感染者总数约为4000万。 自从1989年HCV cDNA首次被克隆成功至今,对HCV的分子生物学研究取得了突飞猛进的发展。目前已明确,HCV为单股正链RNA病毒,属黄病毒科,全长约9600个核苷酸,ORF区编码3010个氨基酸的多聚蛋白前体,经过宿主和病毒本身基因编码的蛋白酶裂解为十个功能性片段,其中四个为结构蛋白,分别是核心蛋白C、包膜蛋白E1、E2以及P7;六个为非结构蛋白,分别是NS2、NS3、NS4A、NS4B、NS5A和NS5B。尽管HCV的基本结构已经清楚,但是HCV的防治仍然是世界性的难题,α干扰素和病毒唑联合治疗是唯一的治疗方法,但这种治疗方法只对不到50%的患者显效,且具有费用高、易复发和副作用多等缺陷;尤其是我国流行的HCV—Ⅱ/1b型,对α干扰素的治疗应答最低,因此发展治疗和预防性丙肝疫苗,对于预防HCV感染和控制感染者的病情发展,都具有重要的意义。 HCV NS3蛋白具有丝氨酸蛋白酶和解旋酶活性,参与病毒蛋白翻译后加工,为病毒复制所必须,针对NS3蛋白的T细胞应答与自限性感染关系密切。目前公认位于NS3区的1248—1261位氨基酸残基为CD4~+Th1细胞表位,而且该表位对于MHC限制性具有广谱特异性。本研究以BALB/c小鼠为实验动物模型,以MHCⅡ抗原提
[Abstract]:Hepatitis C is a serious infectious disease which is harmful to human health. The number of people infected with hepatitis C virus (HCV) is about 170 million, accounting for 1-3 percent of the world population. Among the infected population, about 80% became chronic and 20% developed cirrhosis and hepatocellular carcinoma. In China, HCV infection accounts for 3.2% of the total population, estimated to be about 40 million. Since HCV cDNA was cloned for the first time in 1989, the molecular biology of HCV has been developed by leaps and bounds. It has been confirmed that HCV is a single-stranded positive strand RNA virus, belonging to the family flaviridae, with a total length of 9600 nucleotides. The ORF region encodes a polypeptide precursor of 3010 amino acids, and the protease encoded by the host and the virus itself cleavage into ten functional fragments. Four of them were structural proteins, namely, core protein C, envelope protein E _ 1, E _ 2 and P _ 7. Six are non-structural proteins, NS2,NS3,NS4A,NS4B,NS5A and NS5B., respectively. Although the basic structure of HCV is clear, the prevention and treatment of HCV is still a worldwide problem. Interferon 伪 and ribavirin are the only treatment methods, but this treatment is effective in less than 50% of patients and has high cost. Easy to relapse and many side effects and other defects; Especially HCV- 鈪,

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