Amyocarditic coxsackievirus B3 causes myocarditis in immunocompromised mice.

In the present study, we investigated the role of the immune status of the host in the pathogenesis and development of coxsackievirus B3 myocarditis. We compared the disease expression in myocarditic coxsackievirus B3 (CB3M)-infected BALB/c wild-type mice and severe combined immunodeficient (SCID) mice and in amyocarditic coxsackievirus B3 (CB3O)-infected BALB/c wild-type mice untreated or treated with immunosuppressive agents and SCID mice. There were no differences in viral growth in vitro between CB3M and CB3O. Severe myocarditis developed in CB3M-infected wild-type and SCID mice, CB3O-infected SCID mice and CB3O-infected wild-type mice with total immunosuppression. However, myocarditis was not induced in CB3O-infected wild-type mice untreated and treated with partial immunosuppression. There were no changes in myocardial virus titres among these groups of mice. In addition, myocarditis was induced in CB3O-infected wild-type mice treated with Thy 1.2 (pan T) or Lyt 2 (CD8) antibody but not in those mice treated with L3T4 (CD4) antibody. Thus, the CB3O variant did not induce myocarditis in wild-type mice associated with the induction of the CD8(+) lymphocyte subset but was shown to have the genetic capability to induce myocarditis if the host was in an almost total immunosuppressive or CD8-depleted state. The results suggest that induction of myocarditis by the amyocarditic strain of coxsackievirus B3 may occur and partially depends on the immune status of the host, and that myocarditis is due in part to an immunopathogenic mechanism.