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Differential expression of interferon-induced microRNAs in patients with chronic hepatitis C virus infection treated with pegylated interferon alpha

机译:聚乙二醇化干扰素α治疗慢性丙型肝炎病毒感染患者中干扰素诱导的微小RNA的差异表达

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摘要

There have been reports of in-vitro interferon (IFN)-mediated antiviral activity against the hepatitis C virus (HCV) through microRNAs (miRNAs). The main aim of this study was to evaluate the expression of several miRNAs (miR-1, miR-30, miR-128, miR-196, miR-296) in peripheral blood mononuclear cells (PBMCs) from healthy individuals after in vitro IFN-treatment and in PBMCs from patients with chronic hepatitis C (CHC) before and 12 hours after the first injection of pegylated IFN alpha. We demonstrated that expression of these miRNAs could be recorded in PBMCs collected from healthy individuals before and after in-vitro IFN alpha treatment. Our analysis revealed that the levels of expression of all miRNAs investigated in patients with CHC were different to those in healthy individuals. When levels of the miRNAs were measured 12 hours after the first IFN injection, increases in expression levels of IFN-induced miRNAs were observed in 25-50% of patients, depending on the type of miRNA examined. No correlations were observed between HCV viral load, alanine aminotransferase status and expression of miRNA. Together these findings suggest that: (i) IFN alpha in-vitro treatment of PBMCs leads to a transcriptional induction of all miRNAs investigated; (ii) miRNAs can be induced differentially by IFN treatment in patients with HCV. Given the importance of miRNAs in defending the host against virus infections, it is possible that IFN-induced miRNAs may represent an important determinant of the clinical outcome of IFN therapy in HCV infection.
机译:已有报道通过微RNA(miRNA)体外干扰素(IFN)介导的抗丙型肝炎病毒(HCV)的抗病毒活性。这项研究的主要目的是评估体外干扰素后健康人外周血单个核细胞(PBMC)中几种miRNA(miR-1,miR-30,miR-128,miR-196,miR-296)的表达-首次注射聚乙二醇化IFNα之前和之后12小时,对慢性丙型肝炎(CHC)患者进行PBMC治疗和治疗。我们证明了这些miRNA的表达可以在体外IFNα治疗前后从健康个体收集的PBMC中记录。我们的分析表明,在CHC患者中研究的所有miRNA的表达水平与健康个体不同。在首次注射IFN后12小时测量miRNA的水平时,根据所检查的miRNA的类型,在25-50%的患者中观察到IFN诱导的miRNA的表达水平增加。 HCV病毒载量,丙氨酸转氨酶状态与miRNA表达之间没有相关性。这些发现共同表明:(i)PBMC的IFNα体外治疗导致所有研究的miRNA的转录诱导; (ii)在HCV患者中,可以通过IFN治疗差异诱导miRNA。鉴于miRNA在防御宿主抵抗病毒感染中的重要性,IFN诱导的miRNA可能代表HCV感染中IFN治疗的临床结果的重要决定因素。

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