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Coxsackievirus A10 (CV-A10) has been one of the main etiologies of hand, foot, and mouth disease (HFMD) epidemics in recent years and can cause mild to severe illness and even death. Most of these severe and fatal cases were closely associated with neurological impairments, but the potential mechanism of neuropathological injury triggered by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a post-transcriptional manner, play a vital role in the pathogenesis of various central nervous system (CNS) diseases; therefore, they serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights into the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected human umbilical vein endothelial cells (HUVECs) and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could induce 189 and 302 significantly differentially expressed miRNAs in HUVECs at 24 and 72 hpi, respectively, compared with the uninfected control. Moreover, the expression of four selected miRNAs and their relevant mRNAs was determined to verify the sequencing data by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) methods. After that, gene target prediction and functional annotation revealed that the targets of these dysregulated miRNAs were mostly enriched in cell proliferation, signal transduction, cAMP signalling pathway, cellular response to interleukin-6, ventral spinal cord interneuron differentiation, negative regulation of glial cell differentiation, neuron migration, positive regulation of neuron projection development, etc., which were primarily involved in the processes of basic physiology, host immunity, and neurological impairments and further reflected vital regulatory roles of miRNA in viral pathogenicity. Finally, the construction of a miRNA-regulated network also suggested that the complex regulatory mechanisms mediated by miRNAs might be involved in viral pathogenesis and virus-host interactions during CV-A10 infection. Furthermore, among these dysregulated miRNAs, miR-143-3p was demonstrated to be involved in the maintenance of blood-brain barrier (BBB) integrity. [ABSTRACT FROM AUTHOR]

Introduction: Hand, foot, and mouth disease (HFMD) is a common viral childhood illness, that has been a severe public health concern worldwide, particularly in the Asia-Pacific region. According to epidemiological data of HFMD during the past decade, the most prevalent causal viruses were enterovirus (EV)-A71, coxsackievirus (CV)-A16, CV-A6, and CV-A10. The public health burden of CV-A10-related diseases has been underestimated as their incidence was lower than that of EV-A71 and CV-A16 in most HFMD outbreaks. However, cases of CV-A10 infection are more severe, and its genome is more variable, which has alerted the research community worldwide. Areas covered: In this paper, studies on the epidemiology, laboratory diagnosis, clinical manifestations, molecular epidemiology, seroepidemiology, animal models of CV-A10, and vaccines and antiviral strategies against this genotype are reviewed. In addition, the genetic evolution of circulating strains was analyzed. Expert opinion: Multivalent vaccines against EV-A71, CV-A16, CV-A6, and CV-A10 should be a next-step HFMD vaccine strategy. [ABSTRACT FROM AUTHOR]