Scientists Lifting the Veil of Mystery on the Occasional Nail shedding Associated with Hand, Foot, and Mouth Disease

Hand-foot-and-mouth disease (HFMD) is a prevalent viral infection among children, often manifesting with sores in the mouth and a rash on the hands and feet. Onychomadesis (nail shedding) is a common pathological phenomenon post-HFMD. Until now, the mechanisms driving this sequela were poorly understood, making prevention and treatment challenging. Recently, Professor George Fu Gao's group from the Institute of Microbiology of the Chinese Academy of Sciences uncovered the connection between virus-receptor interaction and pathologic phenomenon through modulation of cell signaling, establishment of links between Coxsackievirus A10 (CV-A10) infection and post-HFMD onychomadesis. This study highlights the activation of the Wnt pathway as a potential treatment and offers novel insights into virus-host cellular signaling interactions. This work was published in Journal of Experimental Medicine.

From the perspective of previous structural study, researchers found that CV-A10 infection mimics the action of a known regulatory protein, Dickkopf-related protein 1 (DKK1), which is crucial in managing Wnt/β-catenin signaling involved in nail growth. By mimicking DKK1, CV-A10 binds to its receptor KREMEN1 and interferes with the Wnt/β-catenin signaling pathway by inhibiting LRP6 phosphorylation and β-catenin accumulation. This interference leads to dysfunction of cell proliferation and nail stem cell differentiation, which consequently manifests as onychomadesis. Importantly, they provide convincing evidence that activation of Wnt signaling with the small molecule CHIR99021 could rescue nail stem cell differentiation in digit tips and holds promising potential as an effective treatment for onychomadesis.

The study was joined forces with Professor CHEN Ye-Guang’s group from Tsinghua University and Professor GAO Shan from Southeast University.

This work was supported by the National Key R&D Program of China and the National Natural Science Foundation of China.

Figure: Proposed model of onychomadesis post-CV-A10 infection. (Image by Prof. George Fu Gao’s Group)