skip to main content
Show Results with:

Die Bedeutung des Immunoproteasoms in der Pathogenese der murinen Coxsackievirus B3 Myokarditis : The impact of the immunoproteasome in murine Coxsackievirus B3 myocarditis

Full text available

  • Title:
    Die Bedeutung des Immunoproteasoms in der Pathogenese der murinen Coxsackievirus B3 Myokarditis : The impact of the immunoproteasome in murine Coxsackievirus B3 myocarditis
  • Author: Voigt, Antje
  • Contributor: Prof. Dr, Martin Scheffner
  • Subjects: 610 Medizin Und Gesundheit ; 610 Medical Sciences; Medicine ; Ddc:610 ; Proteasome ; Virus ; Myocarditis ; Inflammation ; Antigen Processing
  • Publication Details: Berlin: Freie Universität Berlin Universitätsbibliothek
  • Language: German
  • Description: Coxsackie viruses are frequent triggers of myocarditis in humans, a condition that can lead to dilatative cardiomyopathy. The mouse model of Coxsackie virus B3 (CVB3) myocarditis is effectively applicable for study of susceptibility factors that identify patients at risk for chronic illness. Effective virus clearance in CVB3-infected mice requires the induction of a CVB3-specific CD8+ T cell-mediated immune response. Prompt induction of type-I interferons (IFNs) leads in the early phase of CVB3 myocarditis to maturation, activation, and migration of antigen-presenting dendritic cells, and induces in cardiomyocytes as target cells of the virus infection the expression of the MHC class-I antigen presentation machinery. In the heart, this results in assembly of the immunoproteasome that is responsible for an accelerated substrate turnover rate. In the course of these developments, efficiency enhancement of epitope processing becomes apparent for the antigens CVB3 peptide VP2(285-293) and P3D(2170-2177). The type-I IFN response in resistant C57BL/6 mice is associated with virus elimination in accordance with the acute phase of illness. In contrast, haplotype-identical susceptible A.BY/SnJ mice demonstrate markedly acute inflammation and are characterized by a chronic course of disease with virus persistence. The type-I IFN response in these mice, only rudimentarily pronounced, is evidently causative for DC maturation defects and the diminished myocardial immunoproteasome function in the early phase of myocarditis in this strain. The elementary significance of the immunoproteasome assembly and the resulting increase in catalytic activity of the protease in all cells subject to a cytokine-IFN response becomes apparent here, primarily by the protein synthesis ubiquitously increased in this context. The additional formation of ROS in the IFN response leads to oxidative damage of the newly formed proteins in the DRiP pool. Under these conditions, the 26S immunoproteasome can meet the augmented processing requirements in the cell; it regulates the protein homeostasis in IFN-exposed cells. In virus myocarditis as well, the immunoproteasome protects the heart from the toxic effects of damaged proteins and can in such way stabilize cell vitality in this critical phase of disease. For patients with inflammatory cardiomyopathy, these indicative findings on the function of the immunoproteasome in inflammatory processes form the basis for analysis of single-nucleotide polymorphisms of the immune-subunits of the proteasome for which functional defects are shown and that possibly possess prognostic relevance.
  • Creation Date: 2012

Searching Remote Databases, Please Wait