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分析柯萨奇病毒 A2 感染诱导的小鼠心脏损伤中的 microRNAs。

Analysis of miRNAs Involved in Mouse Heart Injury Upon Coxsackievirus A2 Infection.

机构信息

Department of Gerontology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.

出版信息

Front Cell Infect Microbiol. 2022 Jan 28;12:765445. doi: 10.3389/fcimb.2022.765445. eCollection 2022.

DOI:10.3389/fcimb.2022.765445
PMID:35155276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8831793/
Abstract

Coxsackievirus A2 (CVA2) has recently been constantly detected, and is associated with viral myocarditis in children. Our previous study demonstrated that CVA2 led to heart damage in a neonatal murine model. However, the molecular mechanism of heart injury caused by CVA2 remains largely unknown. Emerging evidence suggests the significant functions of miRNAs in Coxsackievirus infection. To investigate potential miRNAs involved in heart injury caused by CVA2, our study, for the first time, conducted a RNA-seq employing infected mice hearts. In total, 87, 101 and 76 differentially expressed miRNAs were identified at 3 days post infection (dpi), 7 dpi and 7 dpi vs 3 dpi. Importantly, above 3 comparison strategies shared 34 differentially expressed miRNAs. These results were confirmed by quantitative PCR (qPCR). Next, we did GO, KEGG, and miRNA-mRNA integrated analysis of differential miRNAs. The dual-luciferase reporter assay confirmed the miRNA-mRNA pairs. To further confirm the above enriched pathways and processes, we did Western blotting and immunofluorescence staining. Our results suggest that inflammatory responses, T cell activation, apoptosis, autophagy, antiviral immunity, NK cell infiltration, and the disruption of tight junctions are involved in the pathogenesis of heart injury caused by CVA2. The dysregulated miRNAs and pathways recognized in the current study can improve the understanding of the intricate interactions between CVA2 and the heart injury, opening a novel avenue for the future study of CVA2 pathogenesis.

摘要

柯萨奇病毒 A2（CVA2）最近不断被检测到，与儿童病毒性心肌炎有关。我们之前的研究表明，CVA2 在新生鼠模型中导致心脏损伤。然而，CVA2 引起心脏损伤的分子机制在很大程度上尚不清楚。新出现的证据表明 miRNA 在柯萨奇病毒感染中具有重要功能。为了研究可能与 CVA2 引起的心脏损伤有关的 miRNA，我们的研究首次采用感染小鼠心脏进行了 RNA-seq。总共在感染后 3 天（dpi）、7 天和 7 dpi 与 3 dpi 时鉴定出 87、101 和 76 个差异表达的 miRNA。重要的是，以上 3 种比较策略共享 34 个差异表达的 miRNA。这些结果通过定量 PCR（qPCR）得到了验证。接下来，我们对差异 miRNA 进行了 GO、KEGG 和 miRNA-mRNA 整合分析。双荧光素酶报告实验验证了 miRNA-mRNA 对。为了进一步确认上述富集的途径和过程，我们进行了 Western blot 和免疫荧光染色。我们的结果表明，炎症反应、T 细胞激活、细胞凋亡、自噬、抗病毒免疫、NK 细胞浸润和紧密连接的破坏与 CVA2 引起的心脏损伤发病机制有关。本研究中识别出的失调 miRNA 和途径可以提高对 CVA2 与心脏损伤之间复杂相互作用的理解，为未来研究 CVA2 发病机制开辟了新途径。

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