ARGLU1 is a negative regulator of the adenoviral replicative cycle
Bibliographic record
Abstract
ABSTRACT We have previously reported that human adenovirus E1A interacts with ARGLU1, a small disordered cellular protein. The consequences of this interaction for virus replication were unclear. E1A is the first protein produced during adenovirus infection. Via protein-protein interactions, E1A modifies the cellular environment to create optimal conditions for viral replication. To better understand the molecular mechanisms driving viral infection, we further investigated the functional consequences of the interaction between ARGLU1 and E1A. ARGLU1 interacts with E1A directly as determined by a GST-pulldown assay with recombinant proteins. Importantly, ARGLU1 was found to act as a transcriptional repressor when it was localized to viral promoters. Repression was driven by enhanced promoter-proximal RNA polymerase II pausing. Significantly, ARGLU1-induced repression of viral promoters is likely an unintended consequence of ARGLU1 binding to E1A, as a mutant of E1A ( dl 1102), unable to bind to ARGLU1, did not show reduced viral gene expression. Furthermore, ARGLU1 was found to colocalize with E1A in infected cell nuclei. Finally, the binding of E1A to ARGLU1 appears to reduce DNA damage repair in bleomycin-treated and adenovirus-infected cells, suggesting that E1A binding to ARGLU1 is important for DNA damage response inhibition. Overall, this study underscores the complexity of virus-host interactions and reveals a novel role for ARGLU1 during adenoviral infection. IMPORTANCE This study uncovers a novel antiviral role for ARGLU1, known for its involvement in splicing, transcriptional regulation, and DNA damage repair. Our study demonstrates that ARGLU1 functions as a viral restriction factor by reducing virus growth through the inhibition of viral gene expression and enhanced DNA damage response, leading to reduced viral growth. These findings not only highlight an important role for ARGLU1 in host antiviral mechanisms but also emphasize the utility of adenovirus as a tool to uncover critical cellular pathways.
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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) | 0.001 | 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) | 0.002 | 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".