Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Virus Res. 2018 Oct 15;258:1-8. doi: 10.1016/j.virusres.2018.09.006. Epub 2018 Sep 22.
Cellular miRNAs influence Hepatitis C virus (HCV) infection in multiple ways. In this study, we demonstrate that miR-125b-5p is upregulated in HCV infected patient serum samples as well as in HCV infected liver carcinoma cells and is involved in translational regulation of one of its predicted targets, Human antigen R (HuR). We used miRNA mimics and antagomiRs to confirm that HuR is a bonafide miR-125b target. Previously, we have shown that HuR is a positive regulator of HCV replication, whereas we noticed that miR-125b is a negative regulator of HCV infection. As a connecting link between these two observations, we showed that knockdown of miR-125b-5p increased HuR protein levels and rescued HCV replication when the availability of HuR in the cytoplasm was compromised using siRNAs against HuR or an inhibitor of HuR export to the cytoplasm. Overall, the study sheds light on the ability of host cell to use a miRNA as a tool to control virus propagation.
细胞 microRNAs 以多种方式影响丙型肝炎病毒 (HCV) 感染。在这项研究中，我们证明 miR-125b-5p 在 HCV 感染的患者血清样本以及 HCV 感染的肝癌细胞中上调，并参与其预测靶标之一的翻译调节，即人类抗原 R (HuR)。我们使用 miRNA 模拟物和 antagomiRs 来证实 HuR 是 miR-125b 的真正靶标。以前，我们已经表明 HuR 是 HCV 复制的正调节剂，而我们注意到 miR-125b 是 HCV 感染的负调节剂。作为这两个观察结果之间的连接环节，我们表明当使用针对 HuR 的 siRNA 或 HuR 输出到细胞质的抑制剂破坏细胞质中 HuR 的可用性时，miR-125b-5p 的敲低会增加 HuR 蛋白水平并挽救 HCV 复制。总的来说，该研究揭示了宿主细胞利用 microRNA 作为工具来控制病毒传播的能力。
