Characterization of microRNA expression profiles associated with hepatitis B virus replication and clearance in vivo and in vitro
Characterization of microRNA expression profiles associated with hepatitis B virus replication and clearance in vivo and in vitro
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DOI：
10.1111/j.1440-1746.2011.06979.x
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发表时间：
2012-04-01
影响因子：
4.1
通讯作者：
Wei, Lai
中科院分区：
文献类型：
--
作者：
Pan, Xiao-Ben;Ma, Hui;Wei, Lai
背景和目的：α干扰素（IFN-α）是一种被批准用于治疗慢性B型肝炎（CH B）的药物。目前已知microRNA（miRNA）是干扰素介导的抗病毒防御的一部分。我们的目的是表征与B型肝炎病毒（HBV）复制和IFN介导的HBV clearance.Methods：我们研究了细胞miRNA的表达模式诱导HBV复制和/或IFN-α治疗HepG2细胞，并分析了外周血单个核细胞中的miRNA应答CH B患者IFN-α治疗。结果：HepG2.2.15和HepG2细胞中差异表达的miRNA共有223条（> 1.5倍），其中24条高度差异表达（> 5倍）。IFN-α处理12 h后，在HepG2细胞中鉴定出23种完全差异表达的miRNA;而在HepG2.2.15细胞中仅鉴定出5种miRNA。HBeAg或非HBeAg血清转换的患者中的miRNA的调节量相似，而8个miRNA的水平显着差异表达两groups.Conclusions：HBV复制改变miRNA的表达谱，并损害IFN-诱导的miRNA在HepG2细胞的反应。ITN治疗的CHB患者外周血单个核细胞的miRNA表达模式可能与其治疗结果相关。
Background and Aim: Alpha interferon (IFN-alpha) is an approved treatment for chronic hepatitis B (CHB). MicroRNA (miRNA) are currently known as a part of IFN-mediated antiviral defense. We aimed at characterizing the miRNA expression associated with hepatitis B virus (HBV) replication and IFN-mediated HBV clearance.Methods: We investigated the expression patterns of cellular miRNA induced by HBV replication and/or IFN-alpha treatment in HepG2 cells, and also analyzed the miRNA response in peripheral blood mononuclear cells in CHB patients on IFN-a treatment. The differentially expressed miRNA were verified using quantitative real-time polymerase chain reaction and an miRNA expression pattern was classified based on the final virological response.Results: A total of 223 miRNA were differentially expressed (> 1.5 folds) between the HepG2.2.15 and HepG2 cells, including 24 highly differentially expressed miRNA (> 5 folds). With 12 h of IFN-alpha, treatment, 23 totally differentially expressed miRNA were identified in HepG2 cells; whereas only five miRNA were identified in HepG2.2.15 cells. Similar amounts of the miRNA were regulated in patients with HBeAg or non-HBeAg seroconversion; whereas levels of eight miRNA were significantly differentially expressed between the two groups.Conclusions: HBV replication alters miRNA expression profiles and impairs IFN-inducible miRNA response in HepG2 cells. The miRNA expression pattern of peripheral blood mononuclear cells in CHB patients with ITN therapy can be associated with their therapeutic outcome.