Abstract 16850: The Impact of Coxsackievirus Infection on Cardiac Stem Cells and Postnatal Heart Development
Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in young children, but in severe cases it can progress to myocarditis or meningo-encephalitis. The long-term consequences of mild CVB infection are unknown, although CVB antibodies are encountered more frequently in patients with heart failure than in the general population, raising the possibility that this cardiotropic virus could have lasting sequelae even in subclinical infection. Previously we described a mouse model in which early postnatal exposure to doxorubicin depleted c-Kit+ cardiac stem cells (CSCs) and resulted in cardiac dysfunction in adult animals that could only be elicited by a prolonged exercise challenge or experimentally induced myocardial infarction. We and others have shown that CVB infects actively proliferating neural stem cells and induces cell death. In this study, we report that cultured CSCs isolated from neonatal mouse hearts were also susceptible to cytopathic CVB infection. To test the hypothesis that CVB infection might deplete the CSC population in the heart during self-limited infection, we inoculated neonatal BALB/c mice with recombinant CVB expressing eGFP and assessed the effects of viral infection on CSCs. We observed infected CSCs in cardiac tissue as well as a 50% reduction in the number of c-Kit+ cells in adult animals. Our observations indicate that CVB can target CSCs in the neonatal heart, infecting them and triggering their destruction. Similar to our findings in the doxorubicin late-onset heart failure model, we suggest that the loss of CSCs during subclinical CVB infection in early childhood may predispose to late-onset heart failure. Further work is needed to demonstrate the cardiovascular consequences of CSC infection and depletion after neonatal CVB infection.
- © 2011 by American Heart Association, Inc.