基于Ii分子的HCV-NS3 Th1表位基因疫苗的設(shè)計(jì)及功能研究
發(fā)布時間:2018-12-16 11:03
【摘要】:丙型病毒性肝炎是嚴(yán)重危害人類健康的傳染病。全球丙肝病毒(HCV)的感染人數(shù)約為一億七千萬,占世界人口總數(shù)的1—3%。在感染的人群中,約8O%轉(zhuǎn)為慢性,20%發(fā)展為肝硬化和肝細(xì)胞癌;我國的HCV感染者占人口總數(shù)的3.2%,估計(jì)感染者總數(shù)約為4000萬。 自從1989年HCV cDNA首次被克隆成功至今,對HCV的分子生物學(xué)研究取得了突飛猛進(jìn)的發(fā)展。目前已明確,HCV為單股正鏈RNA病毒,屬黃病毒科,全長約9600個核苷酸,ORF區(qū)編碼3010個氨基酸的多聚蛋白前體,經(jīng)過宿主和病毒本身基因編碼的蛋白酶裂解為十個功能性片段,其中四個為結(jié)構(gòu)蛋白,分別是核心蛋白C、包膜蛋白E1、E2以及P7;六個為非結(jié)構(gòu)蛋白,分別是NS2、NS3、NS4A、NS4B、NS5A和NS5B。盡管HCV的基本結(jié)構(gòu)已經(jīng)清楚,但是HCV的防治仍然是世界性的難題,α干擾素和病毒唑聯(lián)合治療是唯一的治療方法,但這種治療方法只對不到50%的患者顯效,且具有費(fèi)用高、易復(fù)發(fā)和副作用多等缺陷;尤其是我國流行的HCV—Ⅱ/1b型,對α干擾素的治療應(yīng)答最低,因此發(fā)展治療和預(yù)防性丙肝疫苗,對于預(yù)防HCV感染和控制感染者的病情發(fā)展,都具有重要的意義。 HCV NS3蛋白具有絲氨酸蛋白酶和解旋酶活性,參與病毒蛋白翻譯后加工,為病毒復(fù)制所必須,針對NS3蛋白的T細(xì)胞應(yīng)答與自限性感染關(guān)系密切。目前公認(rèn)位于NS3區(qū)的1248—1261位氨基酸殘基為CD4~+Th1細(xì)胞表位,而且該表位對于MHC限制性具有廣譜特異性。本研究以BALB/c小鼠為實(shí)驗(yàn)動物模型,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 偽 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,
本文編號:2382229
[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 偽 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,
本文編號:2382229
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