Characterization of 2 Influenza A(H3N2) Clinical Isolates with Reduced Susceptibility to Neuraminidase Inhibitors Due to Mutations in the Hemagglutinin Gene
Bibliographic record
Abstract
Previous studies have shown that amino acid changes in the hemagglutinin (HA) gene of influenza viruses may result in decreased susceptibility to neuraminidase inhibitors (NAIs) in vitro. However, the emergence and characteristics of such HA variants in the clinical setting remain poorly studied. Herein, we report 2 influenza A(H3N2) isolates, from untreated patients, harboring an Arg229-->Ile substitution in the HA1 gene. The Ile229 variants were as sensitive as the Arg229 viruses to zanamivir and oseltamivir in neuroaminidase inhibition assays but were significantly less susceptible (by 60-140-fold) in cell-based assays. Although the Ile229 variants adsorbed less efficiently to Madin-Darby canine kidney (MDCK) cells in kinetic binding assays, they remained very sensitive to zanamivir in ferrets. Our study shows the importance of the HA1 229 residue in virus binding to MDCK cells and confirms the unreliability of cell-based assays in predicting the in vivo susceptibility of HA variants to NAIs.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".