Ubiquitination Is Required for Effective Replication of Coxsackievirus B3
Bibliographic record
Abstract
The importance of the ubiquitin/proteasome pathway (UPP) in viral pathogenesis has become increasingly apparent. We have previously demonstrated that the UPP plays a key role in the replication of coxsackievirus B3 (CVB3), an important human pathogen. We have shown that CVB3 replication is markedly reduced by proteasome inhibitors. To further elucidate the underlying mechanisms by which the UPP regulates CVB3 replication, we examined the delicate interplay between the UPP and CVB3 and focused on the role of ubiquitination in viral lifecycle. We found that proteasome inhibition decreased CVB3 RNA replication, protein synthesis, and viral titers. There were no apparent changes in proteasome activities following CVB3 infection. Interestingly, viral infection led to an accumulation of protein‐ubiquitin conjugates, accompanied by a decreased protein expression of free ubiquitin. These data suggested that protein ubiquitination was activated after infection, implicating an important role of ubiquitination in the UPP‐mediated viral replication and/or protein degradation. Using siRNA, we demonstrated that knockdown of ubiquitin significantly reduced viral protein synthesis, possibly through down‐regulation of protein ubiquitination and subsequent degradation. Finally, we investigated the potential mechanisms of increased ubiquitination by examining several enzymes involved in the process of ubiquitination and deubiquitination. However, no significant changes were observed. Taken together, we conclude that CVB3 infection promotes protein ubiquitination, contributing to effective viral replication. This work is supported by CIHR‐HSFC IMPACT Strategic Training Fellowship and CIHR Michael Smith Fellowship.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".