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Contributions of transgenic mouse studies on the research of hepatitis B virus and hepatitis C virus-induced hepatocarcinogenesis

机译:转基因小鼠研究对乙型肝炎病毒和丙型肝炎病毒诱导的肝癌发生研究的贡献

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摘要

Transgenic mouse technology has enabled the investigation of the pathogenic effects, including those on development, immunological reactions and carcinogenesis, of viral genes directly in living organism in a real-time manner. Although viral hepatocarcinogenesis comprises multiple sequences of pathological events, that is, chronic necroinflammation and the subsequent regeneration of hepatocytes that induces the accumulation of genetic alterations and hepatocellular carcinoma (HCC), the direct action of viral proteins also play significant roles. The pathogenesis of hepatitis B virus X and hepatitis C virus (HCV) core genes has been extensively studied by virtue of their functions as a transactivator and a steatosis inducer, respectively. In particular, the mechanism of steatosis in HCV infection and its possible association with HCC has been well studied using HCV core gene transgenic mouse models. Although transgenic mouse models have remarkable advantages, they are intrinsically accompanied by some drawbacks when used to study human diseases. Therefore, the results obtained from transgenic mouse studies should be carefully interpreted in the context of whether or not they are well associated with human pathogenesis.
机译:转基因小鼠技术可以实时地直接在活生物体内研究病毒基因的致病作用,包括对病毒基因的发育,免疫反应和致癌作用。尽管病毒性肝癌的发生包括多种病理事件序列,即慢性坏死性炎症和随后的肝细胞再生,诱导了遗传改变和肝细胞癌(HCC)的积累,但病毒蛋白的直接作用也起着重要作用。乙型肝炎病毒X和丙型肝炎病毒(HCV)核心基因的发病机理已分别通过其作为反式激活因子和脂肪变性诱导剂的功能进行了广泛研究。特别是,已经使用HCV核心基因转基因小鼠模型很好地研究了HCV感染中脂肪变性的机制及其可能与HCC的关联。尽管转基因小鼠模型具有显着的优势,但是当用于研究人类疾病时,它们固有地伴随着一些缺陷。因此,从转基因小鼠研究中获得的结果应在它们是否与人类发病机理良好相关的背景下进行仔细解释。

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