Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China.
Exp Cell Res. 2018 Aug 15;369(2):197-207. doi: 10.1016/j.yexcr.2018.05.019. Epub 2018 May 21.
Human cytomegalovirus (HCMV) has led to kinds of clinical disorders and great morbidity worldwide, such as sensorineural hearing loss (SNHL), mental retardation, and developmental delays in immunocompromised individuals. Congenital HCMV infection is a leading cause of birth defects, primarily manifesting as neurological disorders. Previous studies reported that HCMV has evolved a variety of mechanisms to evade the immune system, such as dysregulation of miRNAs. However, reports concerning the role of miRNA in HCMV infection in neural cells are limited. Here, we reported that a host microRNA, miR-182, was significantly up-regulated by HCMV infection in U-251MG and NPCs cells. Subsequently, our results of in vitro and in vivo experiments demonstrated that miR-182 was a positive regulator of interferon regulatory factor 7 (IRF7) by directly targeting FOXO3, resulting in the induction of IFN-I response and suppression of HCMV replication in neural cells. Taken together, our findings provide detailed molecular mechanisms of the antiviral function of miR-182 against HCMV infection in neural cells, and suggest an intrinsic anti-HCMV therapeutic target.
人巨细胞病毒（HCMV）在全球范围内导致了多种临床疾病和高发病率，如感觉神经性听力损失（SNHL）、智力迟钝和免疫功能低下者的发育迟缓。先天性 HCMV 感染是出生缺陷的主要原因，主要表现为神经紊乱。先前的研究报告称，HCMV 已经进化出多种逃避免疫系统的机制，如 miRNA 的失调。然而，关于 miRNA 在神经细胞中的 HCMV 感染中的作用的报告是有限的。在这里，我们报告说，宿主 microRNA，miR-182，在 U-251MG 和 NPCs 细胞中被 HCMV 感染显著上调。随后，我们的体外和体内实验结果表明，miR-182 通过直接靶向 FOXO3 成为干扰素调节因子 7（IRF7）的正调节剂，导致 IFN-I 反应的诱导和神经细胞中 HCMV 复制的抑制。总之，我们的研究结果提供了 miR-182 对神经细胞中 HCMV 感染的抗病毒作用的详细分子机制，并提示了一种内在的抗 HCMV 治疗靶标。
