PROTEASOMAL PROTEIN DEGRADATION: ADAPTATION OF CELLULAR PROTEOLYSIS WITH IMPACT ON VIRUS- AND CYTOKINE-MEDIATED DAMAGE OF HEART TISSUE DURING MYOCARDITIS.
- 1Charité Universitätsmedizin Berlin, Germany
Viral myocarditis is an inflammation of the heart muscle triggered by direct virus-induced cytolysis and immune response mechanisms with most severe consequences during early childhood. Acute and long-term manifestation of damaged heart tissue and disturbances of cardiac performance involve virus-triggered adverse activation of the immune response and both immunopathology as well as autoimmunity account for such immune-destructive processes. It is a matter of ongoing debate to what extent subclinical virus infection contributes to the debilitating sequelae of the acute disease. In this review, we conceptualize the many functions of the proteasome in viral myocarditis and discuss the adaptation of this multi-catalytic protease complex together with its implications on the course of disease. Inhibition of proteasome function is already highly relevant as a strategy in treating various malignancies. However, cardiotoxicity and immune-related adverse effects have proven significant hurdles, representative of the target’s wide-ranging functions. Thus, we further discuss the molecular details of proteasome-mediated activity of the immune response for virus-mediated inflammatory heart disease. We summarize how the spatiotemporal flexibility of the proteasome might be tackled for therapeutic purposes aiming to mitigate virus-mediated adverse activation of the immune response in the heart.
Keywords: virus, immunoproteasome, cytokine, immunopathology, Myocarditis
Received: 19 Sep 2018;
Accepted: 24 Oct 2018.
Edited by:Michael H. Lehmann, Ludwig Maximilian University of Munich, Germany
Reviewed by:Jason B. Weinberg, University of Michigan, United States
George W. Booz, University of Mississippi Medical Center School of Dentistry, United States
Copyright: © 2018 Beling and Kespohl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Antje Beling, Charité Universitätsmedizin Berlin, Berlin, Germany, firstname.lastname@example.org