Cellular transcriptomics of arrested normal lung fibroblasts IMR-90 infected with Human Adenovirus 5 E1A mutants
Bibliographic record
Abstract
Induction of S-phase is paramount to the replication of most human DNA viruses. Human adenoviruses have evolved sophisticated mechanisms that drive the infected cells into S-phase to ensure that viral genomes are efficiently replicated. We have identified an E1A mutant, E1A289Rdl2-11/YC, that disrupts the canonical means of S-phase induction by E1A. Specifically, this mutant abrogates binding of E1A to the E2F/DP complex as well as to the retinoblastoma protein. Yet, we show that this mutant can still effectively drive the infected cell into S-phase. We explore potential mechanisms of how this occurs via cellular transcriptomic analysis 16 hours after infection. We show that this mutant induces many cell-cycle specific genes to drive S-phase. Interestingly, MYC mRNA is significantly upregulated by this mutant as compared to other viruses investigated. This MYC upregulation, together with normal expression of E4orf6/7 in this mutant, may contribute to efficient S-phase induction. We also demonstrate that this mutant is unable to effectively suppress innate immune response to infection, likely due to loss of p300/CBP binding caused by deletion of E1A residues 2 to 11.
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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 | 0.000 |
| 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".