Distinct kinetics of viral replication, T cell infiltration, and fibrosis in three phases of myocarditis following Theiler’s virus infection

• We established a novel model of myocarditis induced with a cardiovirus.
• Myocarditis was divided into three phases: viral, immune, and fibrotic phases.
• Changes in B-mode and M-mode of echocardiography in viral myocarditis.
• Correlation between viral RNA in the heart and serum cardiac troponin levels.
• IL-6, IL-17, and TLR4 were associated with myocarditis susceptibility.

We established a novel model of myocarditis induced with Theiler’s murine encephalomyelitis virus (TMEV), which has been used as a viral model for multiple sclerosis and seizure/epilepsy. Following TMEV infection, C3H mice developed severe myocarditis with T cell infiltration, while C57BL/6 mice had mild lesions and SJL/J mice had no inflammation in the heart. In C3H mice, myocarditis was divided into three phases: acute viral, subacute immune, and chronic fibrotic phases. Using toll-like receptor (TLR) 4-deficient C3H mice, we found that interleukin (IL)-6, IL-17, TLR4, and anti-viral immune responses were associated with myocarditis susceptibility.