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微小 RNA-324-3p 在柯萨奇病毒 B3 诱导的病毒性心肌炎中发挥保护作用。

MicroRNA-324-3p Plays A Protective Role Against Coxsackievirus B3-Induced Viral Myocarditis.

机构信息

School of Medicine College, Jiangsu University, Zhenjiang, 212013, China.

Xuzhou Municipal Center for Disease Control and Prevention, Xuzhou, 221006, China.

出版信息

Virol Sin. 2021 Dec;36(6):1585-1599. doi: 10.1007/s12250-021-00441-4. Epub 2021 Oct 11.

Abstract

Viral myocarditis (VM) is an inflammatory disease of the myocardium associated with heart failure, which is caused by common viral infections. A majority of the infections are initiated by coxsackievirus B3 (CVB3). MicroRNAs (miRNAs) have a major role in various biological processes, including gene expression, cell growth, proliferation, and apoptosis, as well as viral infection and antiviral immune responses. Although, miRNAs have been found to regulate viral infections, their role in CVB3 infection remains poorly understood. In the previous study, miRNA microarray results showed that miR-324-3p expression levels were significantly increased when cells and mice were infected with CVB3. It was also found that miR-324-3p downregulated TRIM27 and decreased CVB3 replication in vitro and in vivo. In vitro, analysis of downstream signaling of TRIM27 revealed that, miR-324-3p inhibited CVB3 infection, and reduced cytopathic effect and viral plaque formation by reducing the expression of TRIM27. In vivo, miR-324-3p decreased the expression of TRIM27, reduced cardiac viral replication and load, thereby strongly attenuating cardiac injury and inflammation. Taken together, this study suggests that miR-324-3p targets TRIM27 to inhibit CVB3 replication and viral load, thereby reducing the cardiac injury associated with VM.

摘要

病毒性心肌炎 (VM) 是一种与心力衰竭相关的心肌炎症性疾病,由常见的病毒感染引起。大多数感染是由柯萨奇病毒 B3 (CVB3) 引起的。微小 RNA (miRNA) 在各种生物学过程中发挥重要作用,包括基因表达、细胞生长、增殖和凋亡,以及病毒感染和抗病毒免疫反应。虽然已经发现 miRNA 可以调节病毒感染,但它们在 CVB3 感染中的作用仍知之甚少。在之前的研究中,miRNA 微阵列结果表明,当细胞和小鼠感染 CVB3 时,miR-324-3p 的表达水平显著升高。还发现 miR-324-3p 下调了 TRIM27,并减少了体外和体内的 CVB3 复制。在体外,对 TRIM27 的下游信号进行分析表明,miR-324-3p 通过降低 TRIM27 的表达来抑制 CVB3 感染,减少细胞病变效应和病毒斑形成。在体内,miR-324-3p 降低了 TRIM27 的表达,减少了心脏的病毒复制和负荷,从而强烈减轻了心脏损伤和炎症。总之,这项研究表明,miR-324-3p 通过靶向 TRIM27 抑制 CVB3 复制和病毒载量,从而减少与 VM 相关的心脏损伤。

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