The circRNA circSIAE Inhibits Replication of Coxsackie Virus B3 by Targeting miR-331-3p and Thousand and One Amino-Acid Kinase 2.
The circRNA circSIAE Inhibits Replication of Coxsackie Virus B3 by Targeting miR-331-3p and Thousand and One Amino-Acid Kinase 2.
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DOI：
10.3389/fcimb.2021.779919
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发表时间：
2021
影响因子：
5.7
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Yang Q;Li Y;Wang Y;Qiao X;Liu T;Wang H;Shen H
柯萨奇病毒B3(CVB3)是一种肠道病毒，是引起病毒性心肌炎、心包炎、肝炎等炎症相关疾病的主要病原体。具有闭合环分子结构的非编码RNA称为环状RNAs(CircRNAs)，已被证明参与了多种病毒相关过程，但在CVB3感染中的作用和机制尚未得到系统的研究。实时荧光定量聚合酶链式反应检测显示，CVB_3感染HeLa细胞后，hSA_CIRC_0000367(CircSIAE)的表达显著降低。我们发现CircSIAE通过直接结合下调miR-331-3p的表达，并抑制CVB3在HeLa和293T细胞中的复制。对miR-331-3p下游信号的分析表明，miR-331-3p通过与编码一千零一氨基酸激酶2(TAOK2)的基因相互作用，促进CVB3复制、病毒空斑形成和荧光病毒细胞产生。综上所述，本研究发现CircSIAE可以通过海绵吸附miR-331-3p靶向TAOK2，从而抑制CVB3病毒的复制和增殖，为CVB3感染的早期诊断提供了分子靶点。
Coxsackie virus B3 (CVB3), an enterovirus, is the main pathogen causing viral myocarditis, pericarditis, hepatitis and other inflammation-related diseases. Non-coding RNAs with a closed loop molecular structure, called circular RNAs (circRNAs), have been shown to be involved in multiple virus-related processes, but roles and mechanisms in CVB3 infection have not been systematically studied. In this study, when HeLa cells were infected with CVB3, the expression of hsa_circ_0000367 (circSIAE) was significantly decreased as demonstrated by real-time quantitative PCR assays. We found that circSIAE downregulated the expression of miR-331-3p through direct binding and inhibited the replication of CVB3 in HeLa and 293T cells. The analysis of signals downstream of miR-331-3p suggested that miR-331-3p promotes CVB3 replication, viral plaque formation and fluorescent virus cell production through interactions with the gene coding for thousand and one amino-acid kinase 2 (TAOK2). In conclusion, this study found that circSIAE can target TAOK2 through sponge adsorption of miR-331-3p to inhibit the replication and proliferation of CVB3 virus, providing an early molecular target for the diagnosis of CVB3 infection.