Dou Jun, Liu Pengbo, Wang Jing, Zhang Xinjian
Department of Pathogenic Biology and Immunology, Southeast University School of Basic Medical Science, and Department of Obstetrics and Gynecology, affiliated Zhongda Hospital, Nanjing 210009, China.
Cell Mol Immunol. 2006 Jun;3(3):227-33.
In present investigation, we constructed recombinants expressing the HCV genotypes 1b, 2a, and 4d core proteins, and established human hepatocellular carcinoma (HepG2) cell line that expressed various genotype core proteins. The gene expression profiles in the cells expressing different HCV genotype core proteins were compared with those in the control by microarray analysis. In data analysis, a threshold was set to eliminate all genes that were not increased or decreased by 2.5-fold change in a comparison between the transfected cells and control cells. The preliminary microarray analysis suggests that the gene expression profiles regulated by three kinds of genotype core proteins are mainly involved in transport, signal transduction, regulation of transcription, protease activity, etc., and that some pathogenesis/oncogenesis gene expressions are up/down- regulated simultaneously in the HepG2 cell line. The data suggest that each core protein has its gene expressions profile and that the profiles are implicated in HCV replication and pathogenesis, which may open up a novel way to understand the function of the HCV variant core proteins biological and their pathogenic mechanism.
在本研究中,我们构建了表达丙型肝炎病毒(HCV)1b、2a和4d基因型核心蛋白的重组体,并建立了表达各种基因型核心蛋白的人肝癌(HepG2)细胞系。通过微阵列分析,将表达不同HCV基因型核心蛋白的细胞中的基因表达谱与对照细胞中的基因表达谱进行比较。在数据分析中,设定一个阈值以排除在转染细胞与对照细胞的比较中变化未达到2.5倍的所有基因。初步的微阵列分析表明,由三种基因型核心蛋白调节的基因表达谱主要涉及转运、信号转导、转录调控、蛋白酶活性等,并且在HepG2细胞系中一些发病机制/肿瘤发生相关基因的表达同时上调/下调。数据表明每种核心蛋白都有其基因表达谱,并且这些谱与HCV复制和发病机制有关,这可能为理解HCV变异核心蛋白的生物学功能及其致病机制开辟一条新途径。