title: The impact of juvenile coxsackievirus infection on cardiac progenitor cells and postnatal heart development.
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.
authors: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America.
authors: Jon
authors: J
authors: Sin
authors: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California, United States of America.
authors: Jenna M
authors: JM
authors: Puccini
authors: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America.
authors: Chengqun
authors: C
authors: Huang
authors: San Diego State Heart Institute, San Diego State University, San Diego, California, United States of America.
authors: Mathias H
authors: MH
authors: Konstandin
authors: Department of Psychology, San Diego State University, San Diego, California, United States of America.
authors: Paul E
authors: PE
authors: Gilbert
authors: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California, United States of America; San Diego State Heart Institute, San Diego State University, San Diego, California, United States of America.
authors: Mark A
authors: MA
authors: Sussman
authors: Donald P. Shiley BioScience Center, San Diego State University, San Diego, California, United States of America.
authors: Roberta A
authors: RA
authors: Gottlieb
authors: The Integrated Regenerative Research Institute (IRRI) at San Diego State University, Cell & Molecular Biology Joint Doctoral Program, Department of Biology, San Diego State University, San Diego, California, United States of America.
authors: Ralph
authors: R
authors: Feuer
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003384:Coxsackievirus Infections / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D005260:Female; D005355:Fibrosis / Q000473:pathology* / Q000821:virology; D006321:Heart / Q000254:growth & development* / Q000821:virology; D006333:Heart Failure / Q000139:chemically induced / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000821:virology; D013234:Stem Cells / Q000166:cytology* / Q000821:virology; D013312:Stress, Physiological