Reactivation of murine cytomegalovirus by cyclophosphamide

Abstract

THE high prevalence of cytomegalovirus (CMV) infection in transplant recipients is well known but our understanding of the risk factors involved is incomplete. It is thought that the role of immunosuppression is probably paramount. In a series of rheumatologic patients followed prospectively after initiation of cyclophosphamide therapy, a significant proportion (43%) developed CMV infection as evidenced by viruria and serologic response1. Since most of these infections were seen in initially seropositive patients, we believe that they represent reactivations of latent (herein defined as an infection in which no virus can be detected by standard plaque assays) or inapparent infection. Presumably, reactivation by immunosuppression also occurs in transplant recipients. Another risk factor for CMV infection in renal transplant recipients is the transfer of kidneys from donors seropositive for CMV into seronegative recipients2,3. We are using the mouse cytomegalovirus (MCMV) model for better understanding of the factors involved in latency and reactivation of this group of herpeslike viruses and have shown that allografting will enhance chronic MCMV infection in the recipients4. We present here further observations on the mouse model, showing that latent MCMV infection can be reactivated by treatment with cyclophosphamide and that the transfer of latently infected spleen cells can lead to infections in recipients. We also show a role for immunosuppression in the latter situation.