Zhang Lianglu, Chen Xiong, Shi Yingying, Zhou Bingfei, Du Chen, Liu Yongjuan, Han Song, Yin Jun, Peng Biwen, He Xiaohua, Liu Wanhong
Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071, China.
Virus Genes. 2014 Dec;49(3):373-82. doi: 10.1007/s11262-014-1114-4. Epub 2014 Sep 12.
Enterovirus 71 (EV71), a major causative agent of hand, foot, and mouth disease, has broken out several times and was accompanied by neurological disease. microRNAs, a class of small non-coding RNAs that are approximately 20 nucleotides long, play important roles in the regulation of various biological processes, including antiviral defense. However, the roles of miRNAs in EV71 replication and pathogenesis are not well understood. In this study, we found that the expression of miR-27a was significantly decreased in EV71-infected cells. Interestingly, the over-expression of miR-27a could inhibit EV71 replication, as measured by virus titration, qPCR, and Western blotting. We identified EGFR mRNA is a bona fide target of miR-27a by computational analysis and luciferase reporter assays. Furthermore, miR-27a could decrease EGFR expression, as measured by qPCR and Western blotting. Moreover, the inhibition of EGFR expression by miR-27a decreased the phosphorylation of Akt and ERK, which facilitate EV71 replication. These results suggest that miR-27a may have antiviral activity against EV71 by inhibiting EGFR.
肠道病毒71型(EV71)是手足口病的主要病原体,已多次爆发并伴有神经系统疾病。微小RNA(miRNA)是一类长度约为20个核苷酸的小非编码RNA,在包括抗病毒防御在内的各种生物过程的调控中发挥重要作用。然而,miRNA在EV71复制和发病机制中的作用尚未完全明确。在本研究中,我们发现miR-27a在EV71感染的细胞中表达显著降低。有趣的是,通过病毒滴定、qPCR和蛋白质印迹法检测发现,miR-27a的过表达能够抑制EV71复制。通过计算分析和荧光素酶报告基因检测,我们确定表皮生长因子受体(EGFR)mRNA是miR-27a的一个真正靶点。此外,通过qPCR和蛋白质印迹法检测发现,miR-27a能够降低EGFR的表达。而且,miR-27a对EGFR表达的抑制作用降低了Akt和ERK的磷酸化水平,而这两者可促进EV71的复制。这些结果表明,miR-27a可能通过抑制EGFR而具有抗EV71的抗病毒活性。