Introduction: Viruses are known to induce apoptosis in their host cells. We studied whether cardiomyocyte apoptosis occurs upon coxsackievirus B3 (CVB3) infection and whether virus-associated apoptosis plays a role in the pathogenesis of experimental myocarditis.
Methods: BALB/c mice were infected with two variants of CVB3 causing either mild or severe myocarditis. Myocardial and serum samples were collected from Day 1 to Day 14 after virus inoculation. Apoptosis was detected in myocardial tissue sections using the terminal transferase-mediated DNA nick end labelling (TUNEL) assay and staining of active caspase 3, and compared with the presence of infectious CVB3 and viral proteins in cardiomyocytes.
Results: Compared with the noninfected control mice, infection with either CVB3 variant resulted in significantly increased cardiomyocyte apoptosis, which peaked on Day 5 after infection. At this time, the average percentages of apoptotic cardiomyocytes were 0.17% (SD 0.04; P=.03) and 0.77% (SD 0.11; P<.01) in mild and severe disease forms, respectively. The amount of apoptosis correlated with titers of infectious CVB3 in the heart muscle. Viral proteins were detected in the TUNEL-positive cells by immunohistochemistry. In the late stages of disease, apoptosis, together with inflammatory infiltrates persisted only in the severe disease form.
Conclusions: CVB3-associated myocardial damage involves cardiomyocyte apoptosis. In the early stages of the disease, it appears to be triggered by viral replication in the cardiomyocytes.