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

Yingzi Cui, Qiaoni Shi, Pu Song, Jianyu Tong, Zhimin Cheng, Hangchuan Zhang, Xiaodan Wang, Yuxuan Zheng, Yao Wu, Meng Wan, Shihua Li, Xin Zhao, Zhou Tong, Zhengquan Yu, Shan Gao, Ye-Guang Chen, George Gao (2024) Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling J Exp Med (IF: 10.6) 221(8)

Abstract

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 lead 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 and protect against nail shedding. 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.© 2024 Cui et al.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153773
http://www.ncbi.nlm.nih.gov/pubmed/38836810
http://dx.doi.org/10.1084/jem.20231512

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