Hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells.
Hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells.
复制标题
Hsa-let-7c-5p 通过病毒颠覆横纹肌肉瘤细胞中的细胞信号传导增强肠道病毒 71 复制
DOI：
10.1186/s13578-017-0135-9
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发表时间：
2017
影响因子：
7.5
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Zhou B;Chu M;Xu S;Chen X;Liu Y;Wang Z;Zhang F;Han S;Yin J;Peng B;He X;Liu W
人类肠道病毒71型（EV71）可引起严重的手足和小鼠疾病，并伴有神经系统并发症。在EV71与宿主相互作用期间，病毒破坏宿主细胞机制以进行自身复制。然而，microrna （mirna）在这一过程中的作用仍然不清楚。结果本研究发现，在ev71感染的横纹肌肉瘤细胞中，miRNA hsa-let-7c-5p显著上调。hsa-let-7c-5p过表达促进病毒复制，hsa-let-7c-5p抑制剂抑制病毒复制。此外，hsa-let-7c-5p靶向丝裂原活化蛋白激酶激酶激酶4 （MAP4K4）并抑制其表达。有趣的是，MAP4K4表达下调导致EV71复制增加。此外，MAP4K4敲低或转染hsa-let-7c-5p模拟物可激活c-Jun nh2末端激酶（JNK）信号通路，而hsa-let-7c-5p抑制剂可抑制该通路的激活。此外，EV71感染促进JNK通路激活，促进病毒复制。结论hsa-let-7c-5p通过抑制MAP4K4的表达促进EV71的复制，这可能与病毒破坏JNK通路有关。这些结果可能揭示了EV71抵抗细胞反应的新机制。此外，这些发现可能有助于开发新的抗病毒策略，用于未来的治疗。
BackgroundHuman enterovirus 71 (EV71) causes severe hand, foot and mouse disease, accompanied by neurological complications. During the interaction between EV71 and the host, the virus subverts host cell machinery for its own replication. However, the roles of microRNAs (miRNAs) in this process remain obscure.ResultsIn this study, we found that the miRNA hsa-let-7c-5p was significantly upregulated in EV71-infected rhabdomyosarcoma cells. The overexpression of hsa-let-7c-5p promoted replication of the virus, and the hsa-let-7c-5p inhibitor suppressed viral replication. Furthermore, hsa-let-7c-5p targeted mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and inhibited its expression. Interestingly, downregulation of MAP4K4 expression led to an increase in EV71 replication. In addition, MAP4K4 knockdown or transfection with the hsa-let-7c-5p mimic led to activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, whereas the hsa-let-7c-5p inhibitor inhibited activation of this pathway. Moreover, EV71 infection promoted JNK pathway activation to facilitate viral replication.ConclusionsOur data suggested that hsa-let-7c-5p facilitated EV71 replication by inhibiting MAP4K4 expression, which might be related to subversion of the JNK pathway by the virus. These results may shed light on a novel mechanism underlying the defense of EV71 against cellular responses. In addition, these findings may facilitate the development of new antiviral strategies for use in future therapies.