The IFN-Independent Response to Virus Particle Entry Provides a First Line of Antiviral Defense That Is Independent of TLRs and Retinoic Acid-Inducible Gene I
Bibliographic record
Abstract
The innate immune system responds to pathogen infection by eliciting a nonspecific immune response following the recognition of various pathogen-associated molecular patterns. TLRs and the RNA helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 recognize foreign nucleic acid within endosomal and cytoplasmic compartments, respectively, initiating a signaling cascade that involves the induction of type I IFN through the transcription factors IFN regulatory factor (IRF) 3 and NF-kappaB. However, a recent paradigm has emerged in which bacterial DNA and double-stranded B-form DNA trigger type I IFN production through an uncharacterized TLR- and RIG-I-independent pathway. We have previously described a response in primary fibroblasts wherein the entry of diverse RNA- and DNA-enveloped virus particles is sufficient to induce a subset of IFN-stimulated genes and a complete antiviral response in an IRF3-dependent, IFN-independent manner. In this study, we show that the innate immune response to virus particle entry is independent of both TLR and RIG-I pathways, confirming the existence of novel innate immune mechanisms that result in the activation of IRF3. Furthermore, we propose a model of innate antiviral immunity in which exposure to increasing numbers of virus particles elevates the complexity of the cellular response from an intracellular, IFN-independent response to one involving secretion of cytokines and activation of infiltrating immune cells.
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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 | 0.003 | 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) | 0.000 | 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".