發(fā)布時(shí)間：2018-06-26 18:44

  本文選題：基因 + 端粒酶��； 參考：《山東大學(xué)》2006年博士論文

【摘要】：背景 乙型肝炎病毒(hepatitis B virus，HBV)于1966年被發(fā)現(xiàn)，是全球性傳染性肝病的主要病因之一。據(jù)世界衛(wèi)生組織報(bào)道，全球共20億人曾感染乙肝病毒，其中3.5億人為慢性乙肝病毒感染者，，這些慢性感染者具有發(fā)展成為慢性活動(dòng)型肝炎、肝硬化和原發(fā)性肝細(xì)胞癌的高度危險(xiǎn)性。每年約有100萬人死于乙肝病毒相關(guān)的疾病及其感染所致的肝衰竭、肝硬化和原發(fā)性肝細(xì)胞癌。我國約有超過50％的居民曾被乙肝病毒感染過，其中8％～15％的人成為慢性感染者。 雖然目前對(duì)于乙肝病毒基因結(jié)構(gòu)和病毒蛋白的研究有了很大的進(jìn)展，但是由于缺乏科學(xué)、實(shí)用的細(xì)胞模型，使乙肝病毒致病機(jī)制的進(jìn)一步研究受到了很大限制，同時(shí)，也使有效的治療方法的研究無法進(jìn)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)這兩種重要結(jié)構(gòu)和功能蛋白尚需要通過更加完善的細(xì)胞模型來進(jìn)一步研究。HBcAg是21-kDa的細(xì)胞內(nèi)蛋白質(zhì)，可以獨(dú)立包裹病毒基因組與多聚酶裝配成顆粒狀病毒顆粒，是形成具有復(fù)制功能的成熟病毒顆粒必不可少的成分。越來越多的研究表明，HBcAg在產(chǎn)生抗體與激活Th細(xì)胞方面具有強(qiáng)大的免疫原性，可以作為不依賴于T細(xì)胞的獨(dú)立抗原。建立穩(wěn)定表達(dá)HBcAg的細(xì)胞模型，不僅有助于體外探索新型的免疫原，促進(jìn)治療性疫苗的研究，對(duì)于了解HBcAg變異對(duì)慢性乙型肝炎的影響亦有重要的意義。而HBxAg在病毒復(fù)制、細(xì)胞癌變過程中具有重要作用。HBxAg能夠反式激活多種病毒和細(xì)胞增強(qiáng)子，并通過與細(xì)胞核內(nèi)多種轉(zhuǎn)錄因子結(jié)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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R373.21

【引證文獻(xiàn)】

相關(guān)期刊論文 前1條

1 李東;申元英;;感染HBV外周血單個(gè)核細(xì)胞的研究進(jìn)展[J];中國醫(yī)藥生物技術(shù);2011年05期

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