Coxsackievirus A10 Impairs Nail Regeneration and Induces Onychomadesis by Mimicking DKK1 to Attenuate Wnt Signaling

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2024 Jun 5

PMID 38836810

Authors

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 Fu Gao

Affiliations

Soon will be listed here.

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.

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