COXSACKIEVIRUS B3-INDUCED MYOCARDITIS - CHARACTERIZATION OF STABLE ATTENUATED VARIANTS THAT PROTECT AGAINST INFECTION WITH THE CARDIOVIRULENT WILD-TYPE STRAIN

Coxsackievirus B3 (CVB3) is the enterovirus most frequently involved i n human myocarditis or dilated cardiomyopathy. Attenuated variants wer e derived from a cardiovirulent CVB3 reactivated from a sequenced, ful l-length cDNA clone, The prophylactic potential of these variants was assessed in SWR/Ola (H-2q) mice. Animals immunized with attenuated var iants of CVB3 were protected from myocarditis when challenged subseque ntly with the cardiovirulent wild-type virus. In contrast to nonimmuni zen controls, the wildtype virus was not isolated from myocardium of p rotected mice, nor was viral RNA detected in myocardium by reverse tra nscription nested polymerase chain reaction. Specific antibody to CVB3 was demonstrated by virus neutralization assay and by indirect immuno fluorescence. The attenuated phenotype of one variant, p14V-1, remaine d stable throughout 20 consecutive passages in SWR mice and induced a markedly lower level of autoantibody against mouse cardiac myosin heav y chain than the cardiovirulent wild type. These data demonstrate that attenuated strains protect against CVB3-induced myocarditis in mice, that the attenuated phenotype is stable, and that they no not persist in myocardium nor induce a significant level of anti-heart antibody ag ainst myosin heavy chain. These attenuants may be the basis of a live vaccine against CVB3 in the prevention of enteroviral heart muscle dis ease.