Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling

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. Examination the gene expression profiles from PBS and Coxsackievirus A10 infection mice digits. Examination the gene expression profiles from PBS+Vaseline and Coxsackievirus A10-Vaseline and Coxsackievirus A10-CHIR treated mice digits.