Dengue Virus NS5 Inhibits Interferon‐α Signaling by Blocking Signal Transducer and Activator of Transcription 2 Phosphorylation
Bibliographic record
Abstract
Type I interferons (interferon [IFN]-alpha/beta) are key mediators of innate antiviral responses. Inhibition of IFN-mediated signal transduction by dengue viruses (DENVs), mosquito-borne flaviviruses of immense global health importance, probably plays a crucial role in determining the outcome of the virus-host interaction. Understanding the molecular basis of IFN antagonism by DENV would therefore provide critical insight into disease pathogenesis and new opportunities for development of antiviral therapies and rationally attenuated vaccines. Here we examine the effects of expression of DENV nonstructural proteins on cellular IFN responses. We show that expression of nonstructural protein 5 (NS5) alone inhibits IFN-alpha, but not IFN-gamma, signaling. Expression of the polymerase domain of NS5 is sufficient to inhibit IFN-alpha signaling. NS5 binds signal transducer and activator of transcription 2 (STAT2) and inhibits its phosphorylation. NS5 alone did not, however, induce degradation of STAT2, which occurs when all nonstructural proteins are expressed together. We conclude that DENV NS5 is a potent and specific type I IFN antagonist.
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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".