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 in vivo 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.
Highlights
Hand, foot, and mouth disease (HFMD) and herpangina are two principal childhood infectious diseases
Our results demonstrated that Coxsackievirus A2 (CVA2) led to heart injury in a neonatal mouse model
Emerging evidence had shown the important function of miRNAs in EV-induced innate immunity and there were numerous reports of miRNAs that are connected to Coxsackievirus infection (Zhu et al, 2021)
Summary
Foot, and mouth disease (HFMD) and herpangina are two principal childhood infectious diseases. Coxsackievirus belongs to a member of the genus Enterovirus (EV) and the family Picornaviridae. Coxsackievirus A2 (CVA2) has been recognized as a considerable etiological agent in the pathogen spectrum of HFMD and herpangina worldwide (Chansaenroj et al, 2017; Ai et al, 2021). In 2012, 4 young children were reported with serious upper respiratory illness due to CVA2 infection in Hong Kong, two of whom died (Yip et al, 2013). In 2009~2013, it was reported that CVA2 emerged as one of the most leading types of the 12 circulating serotypes of EVs arousing HFMD in Jinan, Shandong Province (Guan et al, 2015).
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