Dissecting the cellular landscape and transcriptome network in viral myocarditis by single-cell RNA sequencing

Area of Science:

• Immunology
• Cardiology
• Virology

Background:

• Coxsackievirus B3 (CVB3) infection is a common model for studying viral myocarditis and its progression to dilated cardiomyopathy.
• Viral myocarditis pathogenesis involves complex interactions between immune and nonimmune cardiac cells.

Purpose of the Study:

• To dissect the cellular complexity and intercellular communication in CVB3-induced myocarditis using single-cell RNA sequencing.
• To identify key cell populations and their roles in viral myocarditis and cardiac remodeling.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on heart cells from healthy and CVB3-infected mice.
• Transcriptomic analysis identified distinct cell populations including myeloid cells, T cells, and fibroblasts.
• Intercellular communication networks were analyzed to understand cell-cell signaling.

Main Results:

• Myeloid cells predominantly exhibited an M2 phenotype.
• T cell subsets (Th17, CTLs, Treg) displayed signatures related to cytotoxic functions.
• Fibroblasts were heterogeneous, expressing genes involved in fibrosis and immune regulation.
• Unique intercellular communication pathways and transcription factors modulating cardiac remodeling were identified in myeloid cells and T cells.

Conclusions:

• M2 myeloid cells, T cells, and fibroblasts play significant roles in viral myocarditis pathogenesis.
• These cell types may act independently or cooperatively in the development of CVB3-induced myocarditis and cardiac dysfunction.