Direct Myocardial Injury by Enterovirus: A Central Role in the Evolution of Murine Myocarditis

A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts

“…51 Some studies showed that viral direct effects occur independently of an immune response, 52,53 while other in vivo experiments demonstrated that the immune response contributes to both detrimental and beneficial effects on the host. [54][55][56][57][58] However, the relationship between viral injury and the immune response in myocarditis remains incompletely understood. In this case, it is likely that the immune responses leading to inflammation were comparable only within certain ranges of virus loads and certain timepoints of infections.…”

Cardiac Myosin and the TH1/TH2 Paradigm in Autoimmune Myocarditis

“…61 Exposure of cardiac myosin in the heart may be an important event leading to the onset of disease in the susceptible host. 62 Evidence has shown that in normal myocardium myosin-class II major histocompatibility antigen complexes are present before the induction of autoimmune myocarditis. 63 Induction of myocarditis is seen only with cardiac myosin and not skeletal myosin 23 or other ␣-helical coiled-coil proteins such as tropomyosin (Galvin and Cunningham, unpublished data).…”

Cellular and Immunological Regulation of Viral Myocarditis

“…We know from the mouse models of CVB3 induced myocarditis that immune infiltration is correlated with the amount of virus inoculum, and therefore with the degree of damage that has been mediated by virus. However experiments comparing the susceptibility of various inbred strains of mice to CVB3 induced myocarditis showed that there could be a genetic predisposition to myocarditis severity (McManus et al, 1993). These data suggest that a genetic predisposition of the individual patient to mild or severe myocarditis, combined with viremia and cardiac viral load could act in concert to determine severity and number of myocarditic foci.…”

“…Autoimmune etiologies due to an antiviral response gone awry have been proposed as one of the major causes of pathology (Lv et al, 2011). Regardless, there are numerous publications that suggest a large amount of damage is inflicted by the virus itself, in the murine model, early post-infection, that is correlated with the number of myocarditic lesions spatially coincident with positivity by in situ hybridization for CVB3 genome (Cheung et al, 2008;Chow et al, 1992;Marchant et al, 2009a;McManus et al, 1993). These observations are supported by findings in autopsy cases, particularly in infants (Iwasaki et al, 1985a;Iwasaki et al, 1985b).…”