MOLECULAR MIMICRY, ANTI-COXSACKIEVIRUS B3 NEUTRALIZING MONOCLONAL-ANTIBODIES, AND MYOCARDITIS

Molecular mimicry has been suggested as one mechanism to explain chron ic myocarditis in some murine strains in the postinfectious period fol lowing induction of acute myocarditis by coxsackievirus B3 (CVB3). To test this hypothesis, neutralizing mAbs were generated against a highl y myocarditic CVB3 virus (CVB3(m)). These mAbs neutralized several myo carditic and amyocarditic CVB3 variants by cytopathic effects inhibiti on assays. Data from several experiments suggest that these mAbs recog nize discontinuous epitopes on CVB3, capsid proteins. Several mAbs wer e found to induce cardiopathologic alterations subsequent to i.p. inoc ulation of normal adolescent male CD-1 or C3 H/HeJ mice. Immunocytoche mical assays demonstrated significant binding of two mAbs to the surfa ce of normal cultured murine cardiac fibroblasts. Also, several mAbs w ere shown to participate in C-mediated lysis of normal cardiac fibrobl asts, but this property did not correlate well with cardiopathogenic p otential. The two properties of a mAb that were the best predictors fo r cardiopathogenic potential were the capacity for stimulation of norm al murine fibroblasts to produce a chemoattractant activity for unelic ited murine peritoneal macrophages, and the capacity for recognition o f an epitopes(s) on murine or human cardiac myosins. These data show t hat some anti-CVB3(m) neutralizing mAbs can participate in proinflamma tory reactions in vitro and induce cardiopathologic alterations in viv o, suggesting one mechanism by which CVB3-induced chronic inflammation in murine heart tissues can be sustained in the absence of continued virus replication.