Abstract
Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in infants, but cases of severe infection can manifest in acute myocarditis. Chronic consequences of mild CVB infection are unknown, though there is an epidemiologic association between early subclinical infections and late heart failure, raising the possibility of subtle damage leading to late-onset dysfunction, or chronic ongoing injury due to inflammatory reactions during latent infection. Here we describe a mouse model of juvenile infection with a subclinical dose of coxsackievirus B3 (CVB3) which showed no evident symptoms, either immediately following infection or in adult mice. However following physiological or pharmacologically-induced cardiac stress, juvenile-infected adult mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. Evaluation of the vasculature in the hearts of adult mice subjected to cardiac stress showed a compensatory increase in CD31+ blood vessel formation, although this effect was suppressed in juvenile-infected mice. Moreover, CVB3 efficiently infected juvenile c-kit+ cells, and cardiac progenitor cell numbers were reduced in the hearts of juvenile-infected adult mice. These results suggest that the exhausted cardiac progenitor cell pool following juvenile CVB3 infection may impair the heart's ability to increase capillary density to adapt to increased load.
Highlights
Coxsackieviruses (CV) are common human pathogens that typically cause a self-limited infection and mild symptoms such as fever, rash, and upper-respiratory complications
Following physiological or pharmacologically-induced cardiac stress, juvenile-infected mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. These results suggest that mild Coxsackievirus B (CVB) infection in the young host may impair the ability of the heart to adapt to increased load leading to pathological remodeling later in adult life
To investigate if coxsackievirus B3 (CVB3) infected cardiac progenitor cells (CPCs) in a similar fashion, c-kit+ cells were isolated from juvenile (Day 17 post-birth) or adult mice and cultured in chamber slides with complete CPC growth medium
Summary
Coxsackieviruses (CV) are common human pathogens that typically cause a self-limited infection and mild symptoms such as fever, rash, and upper-respiratory complications. 70– 80% of individuals with end-stage idiopathic dilated cardiomyopathy have detectable levels of CV RNA in the myocardium without any history of antecedent viral myocarditis [7,8,9]. These findings raise the possibility that mild infection with CV can cause subtle but lasting injury, it is unclear whether such enduring damage is immune-mediated or due to virus-mediated cytopathic effects.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
