Tyrosine phosphorylation of IFITM3 blocks an endocytic motif necessary for its complete influenza virus restriction (INM8P.438)
Bibliographic record
Abstract
Abstract Influenza viruses are a major health concern, with seasonal influenza afflicting an average of 5% to 20% of the US population annually. Interferon-induced transmembrane protein 3 (IFITM3) is important for the inhibition of influenza infection by blocking entry of endocytosed viruses into the cytoplasm. However, the exact mechanisms of IFITM3 regulation and antiviral activity are not clearly defined. Tyrosine phosphorylation by Fyn kinase at the N-terminus of IFITM3 has been previously identified, but the effects of this modification are unknown. We observe IFITM3 cell surface retention for phosphorylation-deficient mutants, minimal cell surface localization in Fyn-deficient cells, and cell surface retention as result of Fyn kinase overexpression. These findings are reproduced for both mouse and human IFITM3, and suggest that phosphorylation of tyrosine 20 in both species blocks an endocytosis motif. Accordingly, tyrosine 20 mutants lose anti-influenza virus activity, confirming the role of endosomal localization in the antiviral function of IFITM3. Our findings classify phosphorylation as a negative regulator of IFITM3, and provide important insights towards delineating the mechanisms by which IFITM3 traffics and restricts viral infection.
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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) | 0.002 | 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 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".