不同缺失突变的丙型肝炎病毒核蛋白在大肠杆菌中的表达

发布时间：2018-01-13 04:14

本文关键词：不同缺失突变的丙型肝炎病毒核蛋白在大肠杆菌中的表达　出处：《第四军医大学》2006年硕士论文　论文类型：学位论文

【摘要】：丙型肝炎病毒(hepatitis C virus，HCV)感染已成为全球性的公共卫生问题。WHO 1999年统计表明，全球目前约有1.7亿人感染HCV，约占全球人口的3％。据估计，每年新增HCV感染人数约为300～400万。丙型肝炎最大的特点是高度慢性化，慢性化率为50％～85％。一部分HCV慢性感染者可演化成肝硬化、肝癌等终末期肝病。丙型肝炎病毒高度变异的特性给疫苗的研制带来了极大的困难。由于HCV核蛋白相对保守，不同型和亚型的HCV株之间有共同的体液和细胞免疫抗原位点，，长期以来作为HCV疫苗的备选抗原一直是研究热点。研究发现，HCV核蛋白可以诱导CTL反应及ADCC，但完整的核蛋白在体外表达水平低，用完整的核蛋白基因进行DNA免疫不能诱导小鼠产生高水平的CTL反应。研究者应用多种策略对核蛋白DNA疫苗进行优化，但仍未达到理想效果。核蛋白DNA疫苗在细胞内表达量不足和核蛋白本身对免疫功能的抑制可能是影响核蛋白特异性免疫的两个重要因素。我室曾通过对核蛋白自身进行改造研究，发现核蛋白羧基末端20位氨基酸缺失能提高其真核表达水平，第60～80位氨基酸缺失可明显提高DNA免疫后核蛋白特异性淋巴细胞增殖反应和
[Abstract]:Hepatitis C virus (HCV) infection has become a global public health problem. At present, there are about 170 million people infected with HCV in the world, accounting for about 3% of the global population. It is estimated that the number of new HCV infections is about 300-#number1# each year. The most characteristic of hepatitis C is highly chronic. The chronic rate of hepatitis C virus is 50%. Some of the chronic HCV infected patients can develop into liver cirrhosis, liver cancer and other end-stage liver diseases. The highly variable characteristics of hepatitis C virus bring great difficulties to the development of the vaccine. Because HCV nucleoprotein is relatively conserved, there are common humoral and cellular immune antigen sites among HCV strains of different types and subtypes. HCV nucleoprotein can induce CTL reaction and ADCCs, but the expression level of intact nucleoprotein in vitro is low. DNA immunization with complete nucleoprotein genes did not induce a high level of CTL response in mice. The researchers used a variety of strategies to optimize the nucleoprotein DNA vaccine. The low expression of nucleoprotein DNA vaccine in cells and the inhibition of immune function by nucleoprotein itself may be two important factors affecting the specific immunity of nucleoprotein. White oneself carries on the transformation research. It was found that the deletion of 20 amino acids at the carboxyl terminal of nucleoprotein could improve the eukaryotic expression level, and the deletion of amino acid at the 60,80th position could significantly increase the proliferative response of nucleoprotein specific lymphocytes after DNA immunization.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R373.21

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