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We have developed a mouse model of myocarditis following mouse adenovirus 1 (MAV-1) infection to study the pathogenic mechanisms of this important cause of pediatric myocarditis. Following intranasal infection of neonatal C57BL\/6 mice, we detected viral replication and induction of interferon gamma (IFN-\u03b3) in the hearts of infected mice. MAV-1 caused myocyte necrosis and induced substantial cellular inflammation that was composed predominantly of CD3<jats:sup>+<\/jats:sup>T lymphocytes. Depletion of IFN-\u03b3 during acute infection reduced cardiac inflammation in MAV-1-infected mice without affecting viral replication. We observed decreased contractility during acute infection of neonatal mice, and persistent viral infection in the heart was associated with cardiac remodeling and hypertrophy in adulthood. IFN-\u03b3 is a proinflammatory mediator during adenovirus-induced myocarditis, and persistent adenovirus infection may contribute to ongoing cardiac dysfunction.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Studying the pathogenesis of myocarditis caused by different viruses is essential in order to characterize both virus-specific and generalized factors that contribute to disease. Very little is known about the pathogenesis of adenovirus myocarditis, which is a significant impediment to the development of treatment or prevention strategies. We used MAV-1 to establish a mouse model of human adenovirus myocarditis, providing the means to study host and pathogen factors contributing to adenovirus-induced cardiac disease during acute and persistent infection. The MAV-1 model will enable fundamental studies of viral myocarditis, including IFN-\u03b3 modulation as a therapeutic strategy.<\/jats:p>","DOI":"10.1128\/jvi.02077-14","type":"journal-article","created":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T03:31:00Z","timestamp":1413430260000},"page":"468-479","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis"],"prefix":"10.1128","volume":"89","author":[{"given":"Mary K.","family":"McCarthy","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Procario","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nele","family":"Twisselmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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