Cardiac fibroblasts aggravate viral myocarditis: cell specific coxsackievirus B3 replication

Area of Science:

• Cardiovascular Biology
• Virology
• Immunology

Background:

• Myocarditis is a severe cardiac inflammation often caused by viral infections.
• Leukocyte infiltration into cardiac tissue contributes to myocyte loss and cardiac remodeling.
• Understanding viral replication sources within the heart is crucial for myocarditis pathology.

Purpose of the Study:

• To investigate cardiac fibroblasts, cardiomyocytes, and macrophages as potential sources of viral replication in Coxsackievirus B3 (CVB3) infection.
• To determine the role of cardiac fibroblasts in the pathogenesis of CVB3-induced myocarditis.

Main Methods:

• Infection of C57BL/6j mice with Coxsackievirus B3 (CVB3).
• Analysis of cytokine gene expression (TNF-α, IL-6, MCP-1, IFN-β) in cardiac cells.
• Quantification of viral replication in cardiac fibroblasts, cardiomyocytes, and macrophages post-infection.

Main Results:

• Cardiac fibroblasts showed significantly increased expression of inflammatory and antiviral cytokines compared to cardiomyocytes and macrophages.
• Cardiac fibroblasts exhibited a 132-fold higher CVB3 replication rate than cardiomyocytes (14-fold increase) between 6 and 24 hours post-infection.
• Macrophages reduced viral copy numbers at high concentrations, while low concentrations led to persistent infection.

Conclusions:

• Cardiac fibroblasts are a significant source of viral replication in CVB3-induced myocarditis.
• Fibroblast involvement exacerbates myocarditis pathology and viral load.
• Targeting cardiac fibroblasts may offer a therapeutic strategy for viral myocarditis.