Myocarditis is an inflammatory disease caused by viral infection. Different
subpopulations of leukocytes enter the cardiac tissue and lead to severe
cardiac inflammation associated with myocyte loss and remodeling. Here, we
study possible cell sources for viral replication using three compartments of
the heart: fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j
mice with Coxsackievirus B3 (CVB3) and detected increased gene expression of
anti-inflammatory and antiviral cytokines in the heart. Subsequently, we
infected cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due
to viral infection, the expression of TNF-α, IL-6, MCP-1, and IFN-β was
significantly increased in cardiac fibroblasts compared to cardiomyocytes or
macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts
were infected by CVB3 and displayed a higher virus replication (132-fold
increase) compared to cardiomyocytes (14-fold increase) between 6 and 24 hours
after infection. At higher virus concentrations, macrophages are able to
reduce the viral copy number. At low virus concentration a persistent virus
infection was determined. Therefore, we suggest that cardiac fibroblasts play
an important role in the pathology of CVB3-induced myocarditis and are another
important contributor of virus replication aggravating myocarditis