Influenza A virus NS1 protein mimics oncogenic PI3K resulting in isoform specific cellular redistribution and activation
Bibliographic record
Abstract
The nonstructural protein 1 (NS1) of influenza A virus performs a broad variety of proviral activities in the infected cell, primarily mediating evasion from the host innate immune response by being the main viral interferon antagonist. However, there are several interactions whose biological relevance remains obscure, such as the ability of NS1 to bind and activate class IA phosphoinositide 3-kinases (PI3Ks). PI3Ks are highly regulated lipid kinases that act as critical nodes in multiple cell signaling networks and are also important proto-oncogenes. This activation is mediated by NS1 binding specifically to the p85β subunit. To better understand the consequences of this interaction, we developed a bimolecular fluorescence complementation (BiFC) assay to selectively track the different PI3K heterodimers and, using this system, we found that NS1 induces an isoform-specific relocation and activation of the different PI3K heterodimers. We found that clinically relevant oncogenic mutations in both catalytic and regulatory subunits of PI3K could mimic the effect caused by NS1, and partially rescue the loss of viral fitness in a recombinant virus encoding a p85β-binding deficient NS1.
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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 | 0.001 |
| 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".