title: Coxsackievirus-induced myocarditis is dependent on distinct immunopathogenic responses in different strains of mice.
abstract: Myocarditis is defined as an inflammation of the heart muscle and often follows enterovirus infections. Frequently, patients surviving the acute inflammatory stage undergo complete recovery, but myocarditis can result in dilated cardiomyopathy. A murine model of myocarditis has been developed that uses cardiotropic variants of coxsackievirus Group B. Type 3 (CVB3), and either BALB/c (H-2d), MRL+/+ (H-2k), or DBA/2 (H-2d) male mice. Infection of all three mouse strains results in equivalent levels of myocardial inflammation 7 days later. IgG antibodies are detected by immunofluorescent staining in DBA/2 but not BALB/c or MRL+/+ myocardium and correlate with the detection of anti-heart antibodies in the sera of DBA/2 mice by immunofluorescence. CD4+ cell depletion of DBA/2 and MRL+/+ mice prevents myocarditis, but both CD4+ and CD8+ T cells cause cardiac inflammation in BALB/c mice, although CD8+ cells are substantially more pathogenic than CD4+ cells in this strain. No or few CD8+ T cells infiltrate the myocardium of either DBA/2- or MRL+/(+)-infected animals, although this is the predominant T-cell population in BALB/c mice. Apoptosis was measured by terminal deoxynucleotidyl transferase-staining of myocardial sections. No apoptosis was observed in inflamed DBA/2 hearts. Apoptosis was restricted to inflammatory cell infiltrates of infected MRL+/+ hearts, but apoptosis was wide-spread in both the inflammatory cell infiltrates and in myocytes outside inflammatory lesions in BALB/c mice. Atria natriuretic factor (ANF) mRNA expression was only elevated in the left ventricles of BALB/c mice. CD8+ T-cell depletion abrogated the appearance of apoptotic myocytes and ANF mRNA expression. The fact that ventricular ANF production often occurs during cardiac failure suggests that myocardial stress is substantially greater in BALB/c mice than in other strains despite equivalent amounts of cardiac inflammation.
authors.affiliation: Department of Pathology, University of Vermont, Burlington 05405, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Huber
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D003384:Coxsackievirus Infections / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human / Q000276:immunology* / Q000472:pathogenicity; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D019463:Mice, Inbred MRL lpr; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013045:Species Specificity
chemical_list: D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor