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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。
Persistent infection of HepatitisBvirus (HBV) is a major problem affecting human health, and interferon (IFNα) and interferonγ (IFNγ) have the anti-HBV effect. In order to investigate the effect of persistence of HBV on the expression of IFN effector genes, HepG2 cells and HepG2.2.15 cells derived from HepG2 cells and integrated with HBV genome were treated with IFNα or IFNγfor 6h, Of human cDNA microarray detected differences in gene expression profiles of each group. The results confirmed that many genes involved in cell cycle, proliferation and apoptosis, as well as some ESTs and function unknown genes were regulated by IFN. After IFN induction, some genes related to kinases and signal transduction, transcription regulation, antigen presentation and processing were The difference between the two cell lines suggests that HBV affects the IFN-induced cellular gene expression. We further selected some of the genes that were significantly differentially expressed and studied their effects on HBV replication. We found that both Diubiquitin and MyD88 differentially expressed genes after IFN induction in both cell lines Significantly reduced HBV antigen expression, and confirmed that MyD88 can inhibit HBV replication. This will help to reveal the antiviral effect of IFN and the mechanism of persistent HBV infection and lay a foundation for the search of molecular targets for new anti-HBV drugs.