Distinct Signature Type I Interferon Responses are Determined by the Infecting virus and the Target Cell
Bibliographic record
Abstract
BACKGROUND: Type I interferons (IFN) include multiple IFN-alpha subtypes which exhibit considerable amino acid identity and activate the same cell-surface receptor. The promoter regions of the IFN-alpha genes, however, have different transcription factor binding sites, implying differential transcriptional activation. Evolutionary conservation of multiple subtypes may have resulted from external pressures associated with the crucial nature of an IFN response, namely that different viruses that are tropic for different target tissues determine the nature and extent of an IFN response, specifically the IFN-alpha subtype profile. METHODS: Studies were undertaken to examine inducible IFN gene expression profiles in response to infection with single-stranded RNA viruses: Sendai virus (SeV), murine hepatitis virus (MHV-1) and coxsackie virus B3 (CVB3). RESULTS: In vitro, distinct signature profiles of SeV and MHV-1-inducible gene expression for IFN-alpha2, IFN-alpha4 and IFN-alpha5 subtypes in L2 and L929 mouse fibroblast cells, in relation to the extent and kinetics of their induction, were identified. In vivo, whereas A/J mice are highly permissive for both MHV-1 and CVB3 infections and mount a poor IFN response, C57B1/6 mice are relatively resistant to both virus infections and mount a vigorous IFN response. CONCLUSIONS: These data suggest that the infecting virus and the target cell type dictate the extent and signature of inducible type I IFN gene expression. The extent of IFN response to viral infection influences the subsequent biological outcome: a robust IFN response prescribes a level of resistance, whereas a poor IFN response contributes towards a permissive phenotype for infection.
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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 | 0.000 |
| 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 | 0.001 |
| 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".