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忍冬苷编码 microRNA2911 通过靶向 VP1 基因抑制肠道病毒 71 复制。

Honeysuckle-encoded microRNA2911 inhibits Enterovirus 71 replication via targeting VP1 gene.

机构信息

Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China.

Department of Pain, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.

出版信息

Antiviral Res. 2018 Apr;152:117-123. doi: 10.1016/j.antiviral.2018.02.015. Epub 2018 Feb 16.

Abstract

Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease (HFMD) in children and virus infections are associated with severe neurological dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA with extreme stability. Here, we report that MIR2911 directly inhibits EV71 replication by targeting the VP1 gene. Bioinformatics prediction and luciferase reporter assay showed that MIR2911 could target the VP1 gene of EV71. Transfection experiments using synthetic MIR2911 and extracted RNA from HS decoction shown that each of these preparations was capable of inhibiting EV71 VP1 protein expression; however, these preparations did not impact EV71 mutants in which the MIR2911-binding sites were mutated. Furthermore, EV71 replication was increased by antagomirs against MIR2911 in the HS decoction, implying that MIR2911 was physiologically functional in controlling EV71 replication in vitro. These results indicated that, by targeting VP1 gene, MIR2911 may effectively inhibit EV71 replication. Our results also provide a potential novel strategy on the therapy and/or prevention of HFMD originating from EV71 virus infection.

摘要

肠道病毒 71 型(EV71)是儿童手足口病(HFMD)的主要病原体,病毒感染与严重的神经功能障碍甚至死亡有关。MIR2911 是一种金银花编码的非典型 microRNA,具有极高的稳定性。在这里,我们报告 MIR2911 通过靶向 VP1 基因直接抑制 EV71 的复制。生物信息学预测和荧光素酶报告基因检测表明,MIR2911 可以靶向 EV71 的 VP1 基因。使用合成的 MIR2911 和 HS 汤提取的 RNA 进行转染实验表明,这些制剂中的每一种都能够抑制 EV71 VP1 蛋白的表达;然而,这些制剂并没有影响到 MIR2911 结合位点发生突变的 EV71 突变体。此外,在 HS 汤中针对 MIR2911 的反义核苷酸增加了 EV71 的复制,这表明 MIR2911 在体外控制 EV71 复制方面具有生理功能。这些结果表明,MIR2911 通过靶向 VP1 基因,可以有效抑制 EV71 的复制。我们的研究结果还为基于 EV71 病毒感染的手足口病的治疗和/或预防提供了一种新的潜在策略。

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