Comparative Study of the Influence of Proteasome Inhibitor MG132 and Ganciclovir on the Cytomegalovirus-Specific CD8+ T-Cell Immune Response

Cytomegalovirus(CMV) reactivation causes immunopathy, graft malfunction, and even rejection. The traditional anti-CMV drug ganciclovir is not able to prevent reactivation of endogenous virus. Recent studies have found that proteasome inhibitor (PI) is able to suppress CMV replication. In this study we investigated the influence of proteasome inhibitor MG132 and ganciclovir on the CMV-specific CD8(+) T-cell immune response. We found that interferon-gamma (IFN-gamma) production in response to CMV-infected fibroblasts was reduced under the influence of MG132 in a dose-dependent manner. A marked reduction was observed at 0.5 mu M. Likewise, CMV-specific cytotoxicity of CD8(+) T cells was decreased in the presence of MG132. In contrast, the traditional CMV replication inhibitor ganciclovir (10 mu M) had no such effect. These findings might have important implications in reducing CMV-associated immunopathy by altering epitope generation through the application of selective proteasome inhibitors.