ArticleScience translational medicine2015
Severe dystrophic cardiomyopathy caused by the enteroviral protease 2A-mediated C-terminal dystrophin cleavage fragment.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Desmin mutations in cardiomyocytes increase susceptibility to coxsackievirus B3 infection by impairing antiviral IFN-β response and upregulating viral receptors expression.Stem cell research & therapy · 2026Article
- Synthetic bottlebrush block copolymer prevents disease onset in Duchenne muscular dystrophy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Friend or Foe?: The Immune System's Dilemma With Dystrophin Replacement Therapy.JACC. Basic to translational science · 2025Article
- Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice.Nature communications · 2024Article
- Myofilament-based physiological regulatory compensation preserves diastolic function in failing hearts with severe Ca2+ handling deficits.JCI insight · 2024Article
- The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy.Journal of neuromuscular diseases · 2024Article
- Update on enteroviral protease 2A: Structure, function, and host factor interaction.Biosafety and health · 2023Review
- Advancing Precision Medicine in Myocarditis: Current Status and Future Perspectives in Endomyocardial Biopsy-Based Diagnostics and Therapeutic Approaches.Journal of clinical medicine · 2023Review
- Enterovirus-Cardiomyocyte Interactions: Impact of Terminally Deleted Genomic RNAs on Viral and Host Functions.Journal of virology · 2023Article
- Picornavirus Cellular Remodeling: Doubling Down in Response to Viral-Induced Inflammation.Current clinical microbiology reports · 2020Article
- Dysregulation of Calcium Handling in Duchenne Muscular Dystrophy-Associated Dilated Cardiomyopathy: Mechanisms and Experimental Therapeutic Strategies.Journal of clinical medicine · 2020Review
- Article
- Exacerbation of dystrophic cardiomyopathy by phospholamban deficiency mediated chronically increased cardiac CaAmerican journal of physiology. Heart and circulatory physiology · 2018Article
- Cardiac Dysfunction in Duchenne Muscular Dystrophy Is Less Frequent in Patients With Mutations in the Dystrophin Dp116 Coding Region Than in Other Regions.Circulation. Genomic and precision medicine · 2018Article
- Functional Consequences of RNA 5'-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation.Journal of virology · 2017Article
- Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins.Frontiers in microbiology · 2017Review
- Connecting enterovirus infection to dystrophin dysfunction in dilated cardiomyopathy.Annals of translational medicine · 2016Article
- Dystrophin contains multiple independent membrane-binding domains.Human molecular genetics · 2016Article
- Enteroviral proteases: structure, host interactions and pathogenicity.Reviews in medical virology · 2016Review
- Microtubule-Mediated Misregulation of Junctophilin-2 Underlies T-Tubule Disruptions and Calcium Mishandling inJACC. Basic to translational science · 2016Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Enterovirus infection can cause severe cardiomyopathy in humans. The virus-encoded 2A protease is known to cleave the cytoskeletal protein dystrophin. It is unclear, however, whether cardiomyopathy results from the loss of dystrophin or is due to the emergence of a dominant-negative dystrophin cleavage product. We show for the first time that the 2A protease-mediated carboxyl-terminal dystrophin cleavage fragment (CtermDys) is sufficient to cause marked dystrophic cardiomyopathy. The sarcolemma-localized CtermDys fragment caused myocardial fibrosis, heightened susceptibility to myocardial ischemic injury, and increased mortality during cardiac stress testing in vivo. CtermDys cardiomyopathy was more severe than in hearts completely lacking dystrophin. In vivo titration of CtermDys peptide content revealed an inverse relationship between the decay of membrane-bound CtermDys and the restoration of full-length dystrophin at the sarcolemma, in support of a physiologically relevant loss of dystrophin function in this model. CtermDys gene titration and dystrophin replacement studies further established a target threshold of 50% membrane-bound intact dystrophin necessary to prevent mice from CtermDys cardiomyopathy. Conversely, the NtermDys fragment did not compete with dystrophin and had no pathological effect. Thus, CtermDys must be localized to the sarcolemma, with intact dystrophin <50% of normal levels, to exert dominant-negative peptide-dependent cardiomyopathy. These data support a two-hit dominant-negative disease mechanism where membrane-associated CtermDys severs the link to cortical actin and inhibits both full-length dystrophin and compensatory utrophin from binding at the membrane. Therefore, membrane-bound CtermDys is a new potential translational target for virus-mediated cardiomyopathy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.