Coxsackieviral Infection Causes Cytoplasmic Aggregation and Cleavage of TAR DNA Binding Protein‐43
Bibliographic record
Abstract
Coxsackievirus B3 (CVB3) is a positive single‐stranded enterovirus that infects the heart. CVB3 infection can cause myocarditis and lead to dilated cardiomyopathy (DCM). In North America, DCM accounts for approximately 20% of heart failure and sudden death in children and young adults. Recent findings have shown similar molecular pathologies between cardiomyopathies and neurodegenerative diseases. In neurodegenerative diseases such as frontotemporal dementia and amyotrophic lateral sclerosis, insoluble‐cytoplasmic TAR DNA binding protein‐43 (TDP‐43)‐aggregates are a common biomarker contributing directly to pathological disease progression. The importance of insoluble protein aggregates in viral pathogenesis has also been recognized, resembling that of neurodegenerative diseases. However, the significance of TDP‐43 in CVB3‐induced cardiomyopathy remains unstudied. In this study, we investigated the interplay between CVB3 and TDP‐43 using A/J mice, a strain susceptible to virus‐induced cardiomyopathy, and HeLa cell culture models. Our studies demonstrated that CVB3 infection leads to redistribution of nuclear TDP‐43 into cytoplasmic aggregates in a viral protease 2A dependent manner. We also found that viral protease 3C, actively cleaves TDP‐43 at amino acid 327 into two respective cleavage fragments. The respective N‐terminal cleavage fragment inhibited native TDP43 activity in the nucleus as a transcriptional regulator. We conclude that TDP‐43 pathologies in CVB3‐induced cardiomyopathy may be similar to those previously found in neurodegenerative diseases . This work was supported by the Canadian Institutes of Health Research (HL)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".