Project description:Coxsackievirus A10 (CV-A10) constitutes one of the major pathogens of hand, foot, and mouth disease (HFMD), which can cause mild to severe illness and even death. Most of these severe and death cases were closely associated with their neurological impairments, but the underlying mechanism of neuropathological injury induced by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a posttranscriptional manner, play a vital role in the pathogenesis of various central nervous systems (CNS) diseases; thereby they are served as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights in the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected HUVEC cells and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could elicit 189 and 302 significantly differentially expressed miRNAs in HUVEC cells at 24 hpi and 72 hpi, respectively, as compared with the uninfected control.
Project description:Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL-receptor-related protein 6 (LRP6) phosphorylation and β-catenin accumulation and led to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3β inhibitor) CHIR99021 can restore nail stem cell differentiation. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.