title: Comparative study of the influence of proteasome inhibitor MG132 and ganciclovir on the cytomegalovirus-specific CD8(+) T-cell immune response.
abstract: 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-γ (IFN-γ) 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 μM. Likewise, CMV-specific cytotoxicity of CD8(+) T cells was decreased in the presence of MG132. In contrast, the traditional CMV replication inhibitor ganciclovir (10 μM) 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.
authors: Institut für Medizinische Immunologie der Charité, Abteilung Klinische Immunologie, Humboldt-Universität zu Berlin (Charité), Campus Charité Mitte, Berlin, Germany.
authors: Yanjun
authors: Y
authors: Wang
authors: Bin
authors: B
authors: Sun
authors: Hans-Dieter
authors: HD
authors: Volk
authors: Susanna
authors: S
authors: Proesch
authors: Florian
authors: F
authors: Kern
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000821:virology; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000821:virology; D007976:Leupeptins / Q000494:pharmacology*; D014775:Virus Activation; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D007976:Leupeptins; D007371:Interferon-gamma; D015774:Ganciclovir; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde