HCV F蛋白在HCV感染和肝癌发生中的作用

项目名称： HCV F蛋白在HCV感染和肝癌发生中的作用

项目编号： No.30872247

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 任浩

作者单位： 中国人民解放军第二军医大学

项目金额： 32万元

中文摘要： HCV F蛋白是由结构基因Core发生核糖体读码框移位编码的一种蛋白，功能尚未明确。本课题体外表达了F蛋白，证明F蛋白能促进细胞增殖，并能抵抗抵抗TNF-α35825;导的凋亡；HCV F蛋白影响细胞（抑）癌基因表达是个复杂的双向调节过程，它既可以通过增加癌基因c-myc转录水平和降低抑癌基因p53转录来促进感染细胞转化，也能通过增加抑癌基因p21的转录来抑制宿主细胞恶变；进一步通过定点突变、基因替换等方法构建了F蛋白突变体和嵌合体，观察了F蛋白缺失后对病毒复制和感染的影响，结果表明F蛋白缺失不影响病毒的复制翻译及病毒颗粒的包装释放，核心蛋白二级结构的改变对病毒复制和翻译则产生较大影响．本研究解析F蛋白在病毒复制周期中的作用，也为深入研究HCV的慢性化机制和肝癌的防治奠定了一定的理论基础。

中文关键词： HCV；F蛋白；感染；肝癌

英文摘要： Hepatitis C virus (HCV) F protein was synthesized from the ribsomal frameshift of structural core gene, and its function remains unclear. In this study, we expressed the F proein in vitro, and the data showed that F protein could promote cell proliferation, and is resistant to the apoptosis induced by TNF-αF protein has cellular transformation activity through up-regulating oncogene c-myc and down-regulating anti-oncogene p53. While as, F ptotein could inhibit the transformation activity by up-regulating anti-oncogene p21. We also constructed F mutants and chimeras by using site-specific mutagenesis and gene substitution, and observed the replication and infection of HCV in in vitro cell culture model of J6JFH1, with the methods of prepariation of RNA transcripts, transfetion,infection,IFA, real time PCR and so on. The results showed that HCV F protein deficiency did not affect translation of viral replication and packaging of the release of virus particles, the core gene secondary structure changes had a great impact on viral replication and protein expression. The results will be helpful to analyze the function of F protein in the virus replication cycle and HCC development, and also provide theoretical basis for studying the chronic mechanism of HCV and prevention and therapy for HCC.

英文关键词： HCV; F protein;infection; hepatocellular carcinoma