Abstract 87: The Impact of Coxsackievirus Infection on Cardiac Stem Cells and Postnatal Heart Development

Abstract

Coxsackievirus B (CVB) is an enterovirus that causes a self-limited febrile illness in infants, but can also cause myocarditis. Long-term consequences of mild CVB infection are unknown, although an association between heart failure and seropositive status has been previously described. We have shown that early postnatal exposure to doxorubicin depleted c-Kit+ cardiac stem cells (CSCs). Cardiac dysfunction in adult mice only developed after exercise challenge, or experimentally-induced myocardial infarction. We now report that CSCs from neonatal mouse hearts were susceptible to cytopathic CVB infection. To learn if mild CVB infection might deplete the CSC population in the heart, we inoculated newborn BALB/c mice with a recombinant CVB expressing eGFP. We observed CVB-infected CSCs 2 days post-inoculation and documented a reduction in the number of c-Kit+ cells in the hearts of animals at 4 and 11 weeks of age despite the absence of detectable virus. Moreover, CVB infection induced differentiation in the surviving CSCs. These results indicate that CVB can infect CSCs in the neonatal heart and trigger their destruction. Premature differentiation of surviving cells may also explain the reduced CSC population in adult mice. Despite normal histologic features in adult hearts, prolonged exercise challenge elicited cardiac hypertrophy and fibrosis in mice infected with CVB as pups. We suggest that the loss of CSCs after mild neonatal CVB infection may predispose to late-onset heart failure.