Coxsackievirus B₃ murine myocarditis: A pathologic spectrum of myocarditis in genetically defined inbred strains

Group B coxsackieviruses are the most frequent causative agents in human viral myocarditis. Susceptibility to viral infections varies widely among individuals. In the mouse, coxsackievirus B₃ also causes myocarditis. The differential susceptibility of different inbred strains of mice to Coxsackie B₃-induced myocarditis also appears to be under genetic control. This study details the histo-pathology of Coxsackie B₃ myocarditis in six different inbred strains of mice for the first 45 days after Coxsackie B₃ infection. These strains differ either in the haplotypes of their major histocompatibility complex or in their background genome. During the first 7 days after Coxsackie B₃ infection, there are dramatic differences among strains with respect to prevalence and severity of myocarditis. Focal zones of myocyte necrosis involving polymorphonuclear leukocytes as well as contraction band injury appear to be the early manifestations of direct viral injury. Four of the six strains, though, continue to show myocardial inflammation after day 9. This late phase myocarditis is characterized by the emergence of mononuclear cells within healing foci of myocyte necrosis as well as a distinctive diffuse interstitial pattern of myocarditis. The strains that develop this late ongoing myocardial inflammation frequently produce heart-specific autoantibodies. Thus 1) the pathologic features of murine Coxsackie B₃ myocarditis change over the course of the illness, and 2) genetic susceptibility to both early and late phase myocarditis differs markedly among various mouse strains.