Primary cytomegalovirus infection following cardiac transplantation in a murine model

A murine cytomegalovirus (CMV) model was utilized to determine the source of primary CMV infection in cardiac transplantation. Hearts were taken from actively or latently infected BALB/C mice and then transplanted as primary, heterotopic isografts into CMV-negative BALB/C recipients. The transplantation of hearts from acutely infected donors into nonimmunosuppressed recipients resulted in asymptomatic primary infection as manifested by detectable virus in both donor and recipient hearts, liver, spleen, and salivary glands and by the development of anti-CMV antibody. When hearts from latently infected animals were transplanted into nonimmunosuppressed recipients, a transient primary infection occurred that was manifested by detectable virus in the spleen and salivary glands and the appearance of anti-CMV antibody. When recipient animals were immunosuppressed with cortisone acetate (125 mg/kg/day i.p.) and rabbit antimouse thymocyte globulin (0.2 ml i.p. twice weekly), after transplantation of hearts from acutely and latently infected mice, lethal primary CMV infection developed. High titers of virus were recovered in all organs tested in these animals, including both the donor and recipient hearts. We conclude that the heart is infected during the course of primary murine CMV infection, and that hearts from latently infected animals are a source of serious primary infection in immunosuppressed recipients. This experimental system should be a useful model relevant to human cardiac transplantation.