ArticlePLoS pathogens2011
Impairment of immunoproteasome function by β5i/LMP7 subunit deficiency results in severe enterovirus myocarditis.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Corticosteroids for viral myocarditis.The Cochrane database of systematic reviews · 2013Pooled it
- Dissecting myocardial and systemic drivers of cardiac dysfunction in the murine CVB3 myocarditis model using microRNA-guided viral detargeting.Basic research in cardiology · 2026Article
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- PSMB9 exacerbates chondrocyte injury in osteoarthritis via activation of the NF-κB pathway.Journal of orthopaedic surgery and research · 2026Article
- Cellular protein quality control in viral myocarditis: molecular mechanisms and therapeutic implication.Microbiology and molecular biology reviews : MMBR · 2025Review
- The Ubiquitin-Proteasome System: A Key Regulatory Hub in Myocarditis Leading to Dilated Cardiomyopathy.Journal of inflammation research · 2025Review
- Effects of immunoproteasome inhibition on acute respiratory infection with murine hepatitis virus strain 1.Journal of virology · 2024Article
- ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection.Cardiovascular research · 2024Article
- Genetic ablation of Lmp2 increases the susceptibility for impaired cardiac function.Frontiers in molecular biosciences · 2024Article
- Immunoproteasome acted as immunotherapy 'coffee companion' in advanced carcinoma therapy.Frontiers in immunology · 2024Review
- Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling.Frontiers in immunology · 2023Article
- Immunoproteasome Inhibition Ameliorates Aged Dystrophic Mouse Muscle Environment.International journal of molecular sciences · 2022Article
- Airway epithelial immunoproteasome subunit LMP7 protects against rhinovirus infection.Scientific reports · 2022Article
- Disorders of ubiquitylation: unchained inflammation.Nature reviews. Rheumatology · 2022Review
- Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases.Cells · 2022Review
- Biology of the Extracellular Proteasome.Biomolecules · 2022Review
- Microbial proteasomes as drug targets.PLoS pathogens · 2021Review
- Review
- Review
- Role of Proteasomes in Inflammation.Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteasomes recognize and degrade poly-ubiquitinylated proteins. In infectious disease, cells activated by interferons (IFNs) express three unique catalytic subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform, the immunoproteasome (IP). The in vivo function of IPs in pathogen-induced inflammation is still a matter of controversy. IPs were mainly associated with MHC class I antigen processing. However, recent findings pointed to a more general function of IPs in response to cytokine stress. Here, we report on the role of IPs in acute coxsackievirus B3 (CVB3) myocarditis reflecting one of the most common viral disease entities among young people. Despite identical viral load in both control and IP-deficient mice, IP-deficiency was associated with severe acute heart muscle injury reflected by large foci of inflammatory lesions and severe myocardial tissue damage. Exacerbation of acute heart muscle injury in this host was ascribed to disequilibrium in protein homeostasis in viral heart disease as indicated by the detection of increased proteotoxic stress in cytokine-challenged cardiomyocytes and inflammatory cells from IP-deficient mice. In fact, due to IP-dependent removal of poly-ubiquitinylated protein aggregates in the injured myocardium IPs protected CVB3-challenged mice from oxidant-protein damage. Impaired NFκB activation in IP-deficient cardiomyocytes and inflammatory cells and proteotoxic stress in combination with severe inflammation in CVB3-challenged hearts from IP-deficient mice potentiated apoptotic cell death in this host, thus exacerbating acute tissue damage. Adoptive T cell transfer studies in IP-deficient mice are in agreement with data pointing towards an effective CD8 T cell immune. This study therefore demonstrates that IP formation primarily protects the target organ of CVB3 infection from excessive inflammatory tissue damage in a virus-induced proinflammatory cytokine milieu.
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