基因芯片分析干扰素对乙型肝炎病毒转染细胞基因表达的影响(英文)  

Analysis of Gene Expression in Hepatitis B Virus Transfected Cell Line Induced by Interferon

作　　者：熊炜[1] 王迅[1] 刘晓颖[1] 项黎[1] 郑玲洁[1] 刘江霞[1] 袁正宏[1] 

机构地区：[1]复旦大学上海医学院教育部医学分子病毒学重点实验室,上海200032

出　　处：《生物化学与生物物理学报》2003年第12期1053-1060,共8页

基　　金：国家重点基础研究发展规划项目(973计划) (No .1999054105);复旦大学MedX基金;复旦大学研究生创新基金项目资助~~

摘　　要：乙型肝炎病毒 (HepatitisBvirus ,HBV)的持续性感染是影响人类健康的重大问题 ,而α 干扰素 (IFN α)和γ 干扰素(IFN γ)分别具有抗HBV的作用。为了研究HBV持续存在对IFN效应基因表达的影响 ,将HepG2细胞和来源于HepG2细胞并整合有HBV基因组的HepG2 .2 .15细胞经IFN α或IFN γ处理 6h后 ,用含 14 112个靶基因的人cDNA基因芯片检测了各组基因表达谱的差异。结果证实 ,许多与细胞周期、增殖、凋亡相关的基因及部分EST和功能未知基因受IFN调节 ;IFN诱导后 ,一些与激酶和信号转导、转录调节、抗原递呈和处理相关的基因在两株细胞间表达存在差异 ,提示HBV影响IFN诱导的细胞基因的表达。进一步挑选部分显著差异表达的基因 ,研究其对HBV复制的影响 ,结果发现在两个细胞株中IFN诱导后基因表达差异的双遍在蛋白 (Diubiquitin)和髓样细胞分化蛋白 (MyD88)均可显著降低HBV抗原表达 ,并证实MyD88能抑制HBV复制。这有助于揭示IFN抗病毒效应及HBV持续性感染机制 ,为分子水平寻找新型抗HBV药物的靶点打下基础。Infection of hepatitis B virus (HBV) continues to be a significant health problem. α interferon (IFN-α) and γ interferon (IFN-γ) have been proven to be effective in inhibiting HBV replication. To study the global effect of HBV persistent existence on IFN induced cellular gene expression, cDNA microarrays dotted with 14 112 human genes were used to examine the transcriptional changes between an HBV DNA transfected cell line (HepG2.2.15) and its parental cell line (HepG2) after the treatment of IFN-α or IFN-γ for 6 h. The results showed that many genes related to cell cycle, proliferation, apoptosis and new ESTs were regulated by IFN-α and/or IFN-γ. Many genes involved in kinase and signal transduction, transcription regulation, antigen presentation and processing were differentially regulated between these two cell lines post IFN-α or IFN-γ treatment. Interestingly, several IFN-differentially regulated genes, such as MyD88 and Diubiquitin, were found to inhibit HBV gene expression, and MyD88 was proved to inhibit HBV replication. Taken together, our results revealed the global effects of HBV persistent existence on IFN-induced cellular gene expression. The novel antiviral genes identified by microarray could be potentially developed as new anti-HBV drugs or for novel therapies.

关 键 词：干扰素 乙型肝炎病毒 基因芯片 转染细胞 基因表达 HBV 

分 类 号：R346[医药卫生—基础医学]