乙型肝炎病毒核心蛋白及X蛋白在长期培养外周血单个核细胞内的表达

发布时间：2018-06-26 18:44

本文选题：基因 + 端粒酶　；参考：《山东大学》2006年博士论文

【摘要】：背景乙型肝炎病毒(hepatitis B virus，HBV)于1966年被发现，是全球性传染性肝病的主要病因之一。据世界卫生组织报道，全球共20亿人曾感染乙肝病毒，其中3.5亿人为慢性乙肝病毒感染者，，这些慢性感染者具有发展成为慢性活动型肝炎、肝硬化和原发性肝细胞癌的高度危险性。每年约有100万人死于乙肝病毒相关的疾病及其感染所致的肝衰竭、肝硬化和原发性肝细胞癌。我国约有超过50％的居民曾被乙肝病毒感染过，其中8％～15％的人成为慢性感染者。虽然目前对于乙肝病毒基因结构和病毒蛋白的研究有了很大的进展，但是由于缺乏科学、实用的细胞模型，使乙肝病毒致病机制的进一步研究受到了很大限制，同时，也使有效的治疗方法的研究无法进行。尤其是乙肝病毒核心抗原(hepatitis B core antigen，HBcAg)和X抗原(hepatitis B X antigen，HBxAg)这两种重要结构和功能蛋白尚需要通过更加完善的细胞模型来进一步研究。HBcAg是21-kDa的细胞内蛋白质，可以独立包裹病毒基因组与多聚酶装配成颗粒状病毒颗粒，是形成具有复制功能的成熟病毒颗粒必不可少的成分。越来越多的研究表明，HBcAg在产生抗体与激活Th细胞方面具有强大的免疫原性，可以作为不依赖于T细胞的独立抗原。建立稳定表达HBcAg的细胞模型，不仅有助于体外探索新型的免疫原，促进治疗性疫苗的研究，对于了解HBcAg变异对慢性乙型肝炎的影响亦有重要的意义。而HBxAg在病毒复制、细胞癌变过程中具有重要作用。HBxAg能够反式激活多种病毒和细胞增强子，并通过与细胞核内多种转录因子结合
[Abstract]:Background Hepatitis B virus (hepatitis B virus) was discovered in 1966 and is one of the major causes of global infectious liver disease. According to the World Health Organization, a total of 2 billion people worldwide have been infected with hepatitis B virus, of which 350 million have been infected with chronic hepatitis B. these chronic infections have developed into chronic active hepatitis. Liver cirrhosis and primary hepatocellular carcinoma are at high risk. About 1 million people die each year from liver failure, cirrhosis and primary hepatocellular carcinoma due to hepatitis B virus related diseases and their infections. More than 50% of the residents in China have been infected with hepatitis B virus, of which 815% have become chronic infections. Although great progress has been made in the study of HBV gene structure and viral protein, due to the lack of scientific and practical cell models, the further study of the pathogenesis of HBV has been greatly restricted. It also makes it impossible to study effective treatments. In particular, hepatitis B core antigenn HBcAg and hepatitis B X antigenn HBxAg, two important structural and functional proteins, need to be further studied through more perfect cell models. HBcAg is a 21-kDa intracellular protein. The virus genome can be encapsulated independently with polymerase to form granular virus particles, which is an essential component for the formation of mature viral particles with replication function. More and more studies have shown that HBcAg has strong immunogenicity in producing antibodies and activating Th cells and can be used as an independent antigen independent of T cells. The establishment of a cell model of stable expression of HBcAg is not only helpful to explore new immunogen in vitro and promote the research of therapeutic vaccine, but also to understand the effect of HBcAg mutation on chronic hepatitis B. HBxAg plays an important role in viral replication and cell carcinogenesis. HBxAg can transactivate multiple viruses and cell enhancers and bind to multiple transcription factors in the nucleus.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R373.21

【引证文献】