Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome; Rome, Italy.
Virol J. 2010 Nov 12;7:311. doi: 10.1186/1743-422X-7-311.
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.
已有研究报道，通过 microRNAs（miRNAs），体外干扰素（IFN）可介导对丙型肝炎病毒（HCV）的抗病毒活性。本研究的主要目的是评估几种 miRNAs（miR-1、miR-30、miR-128、miR-196、miR-296）在体外 IFN 处理后健康个体外周血单个核细胞（PBMCs）中的表达，以及慢性丙型肝炎（CHC）患者 PBMCs 中在首次聚乙二醇化 IFNα 注射前和 12 小时后的表达。我们证明，可在体外 IFNα 处理前后从健康个体采集的 PBMCs 中记录这些 miRNAs 的表达。我们的分析表明，CHC 患者中所有研究的 miRNAs 的表达水平与健康个体不同。当在首次 IFN 注射后 12 小时测量 miRNA 的水平时，取决于所检查的 miRNA 的类型，在 25-50%的患者中观察到 IFN 诱导的 miRNAs 的表达水平增加。未观察到 HCV 病毒载量、丙氨酸氨基转移酶状态和 miRNA 表达之间存在相关性。总之，这些发现表明：（i）体外 PBMCs 的 IFNα 治疗导致所有研究的 miRNAs 的转录诱导；（ii）IFN 治疗可在 HCV 患者中以不同的方式诱导 miRNA。鉴于 miRNAs 在防御宿主免受病毒感染方面的重要性，IFN 诱导的 miRNAs 可能是 HCV 感染中 IFN 治疗临床结果的重要决定因素。
