Allogeneic Stimulation Causes Transcriptional Reactivation of Latent Murine Cytomegalovirus

Abstract Cytomegalovirus (CMV) reactivation is a well-described complication of transplantation that may be caused by allogeneic stimulation, immunosuppression, or both. These studies were performed to determine if allogeneic stimulation alone is sufficient to reactivate latent CMV. BALB/c mice latently infected with Smith strain murine CMV (MCMV) received allograft (n = 8), allograft plus cortisol (n = 5), or isograft (n = 4) skin. All allograft recipients rejected their grafts within 9 to 12 days of transplantation. Three weeks after grafting, recipients were evaluated for MCMV reactivation, and all allograft recipients (8/8) showed MCMV reactivation, while no isografts had reactivation (0/4). Surprisingly, cortisol therapy blocked MCMV reactivation (0/5). These data suggested that allogeneic stimulation alone can trigger systemic reactivation of latent CMV. Although immunosuppression is thought to contribute to reactivation, certain agents that impair NF-κB activation may actually reduce reactivation.