Mitogen-activated Protein Kinase-mediated Licensing of Interferon Regulatory Factor 3/7 Reinforces the Cell Response to Virus
Bibliographic record
Abstract
The induction of the intrinsic antiviral defense in mammals relies on the accumulation of foreign genetic material. As such, complete engagement of this response is limited to replication-competent viruses. Interferon regulatory factors (IRFs) are mediators of this defense with shared enhancer elements but display a spectrum of transcriptional potential. Here we describe a mechanism designed to enhance this response should a pathogen not be successfully inhibited. We find that activation of IRF7 results in the induction of MAP3K8 and restructuring of the antiviral transcriptome. MAP3K8 mediates the phosphorylation and repression of IRF3 homodimers to promote greater transcriptional activity through utilization of IRF3:IRF7 heterodimers. Among the genes influenced by the MAP3K8/IRF7 signaling axis are members of the SP100 gene family that serve as general transcriptional enhancers of the antiviral defense. We propose that this feed forward loop serves to reinforce the cellular response and is reserved for imminent threats to the host.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.002 | 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 teacher head, 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".