Analyses of myocardial epitopes and apoptosis with treatment of peptide therapy in myocarditis.

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To clarify the pathogenesis and the development of coxsackievirus B3 (CVB3) myocarditis, we examined the histopathology of CVB3-inoculated wild type and severe combined immunodeficient C3H/He mice, and analyzed using subcloning method the sequence of nucleotides of an amyocarditic strain of CVB3 (CVBO) with comparison of that of a myocarditic strain of CVB3 (CVBM), which was already reported. Severe myocarditis developed in wild mice inoculated with CVBM.On the contrary, mild myocarditis resulted from wild mice inoculated with CVBO.In scid mice, severe myocarditis developed by the inoculation of both CVBM and CVBO.There were seven nucleotide differences with five corresponding amino acid changes in the sequence of CVBO in comparison with that of CVBM.The changes located in 1A, 1C, and 1D regions of viral genome, which encoded the envelope protein. Thus, antigenic determinant of CVB3 is related, at least in part, to the recognition of immunocompetent cells to the difference of nucleotides in these regions. In conclusion, the development of myocarditis is related to the immunological background of the host, and myocarditis is due, in part, to an immunopathogenic phenomenon.