本文關(guān)鍵詞：不同缺失突變的丙型肝炎病毒核蛋白在大腸桿菌中的表達　出處：《第四軍醫(yī)大學》2006年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 丙型肝炎病毒 核蛋白 突變 原核表達

【摘要】：丙型肝炎病毒(hepatitis C virus，HCV)感染已成為全球性的公共衛(wèi)生問題。WHO 1999年統(tǒng)計表明，全球目前約有1.7億人感染HCV，約占全球人口的3％。據(jù)估計，每年新增HCV感染人數(shù)約為300～400萬。丙型肝炎最大的特點是高度慢性化，慢性化率為50％～85％。一部分HCV慢性感染者可演化成肝硬化、肝癌等終末期肝病。丙型肝炎病毒高度變異的特性給疫苗的研制帶來了極大的困難。 由于HCV核蛋白相對保守，不同型和亞型的HCV株之間有共同的體液和細胞免疫抗原位點，，長期以來作為HCV疫苗的備選抗原一直是研究熱點。研究發(fā)現(xiàn)，HCV核蛋白可以誘導(dǎo)CTL反應(yīng)及ADCC，但完整的核蛋白在體外表達水平低，用完整的核蛋白基因進行DNA免疫不能誘導(dǎo)小鼠產(chǎn)生高水平的CTL反應(yīng)。研究者應(yīng)用多種策略對核蛋白DNA疫苗進行優(yōu)化，但仍未達到理想效果。核蛋白DNA疫苗在細胞內(nèi)表達量不足和核蛋白本身對免疫功能的抑制可能是影響核蛋白特異性免疫的兩個重要因素。我室曾通過對核蛋白自身進行改造研究，發(fā)現(xiàn)核蛋白羧基末端20位氨基酸缺失能提高其真核表達水平，第60～80位氨基酸缺失可明顯提高DNA免疫后核蛋白特異性淋巴細胞增殖反應(yīng)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.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2006
【分類號】：R373.21

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