COXSACKIEVIRUS-INDUCED CHRONIC MYOCARDITIS IN MURINE MODELS

Challenge of several murine strains with two highly myocarditic varian ts of coxsackievirus B3 (CVB3) induced acute and chronic myocarditis, detectable at 21 and 45 days post-inoculation (p.i.). In-situ hybridiz ation of coronal heart sections showing chronic inflammation with a ra diolabelled CVB3 probe detected viral genomic RNA at day 7 p.i. but ra rely at 21 or 45 days p.i., suggesting few murine heart cells actively replicate virus during chronic myocardial inflammation. Data will be presented that favour an alternative hypothesis, i.e. autoimmune respo nses to shared epitopes among CVB3 proteins cardiac myosin and myocard ial cell surface proteins (molecular mimicry) can affect the severity of chronic inflammation. Mice inoculated with human cardiac myosin (HM ) prior to a CVB3(m) challenge develop less myocarditis than mice inoc ulated with virus only, suggesting that antibodies stimulated by HM bi nd virus, reduce the virus burden and provide protection. Mice inocula ted with HM only develop non-neutralizing antibodies against purified CVB3(m) particles. Several strains of mice inoculated with specific sy nthetic peptides of HM produce antibodies against CVB3(m) and/or devel op cardiomyopathy. Thus antigen-challenged mice can produce antibodies which cross-react among CVB3(m), HM or cardiac cells to protect or ex acerbate heart disease.