Effect of the Neuraminidase Mutation H274Y Conferring Resistance to Oseltamivir on the Replicative Capacity and Virulence of Old and Recent Human Influenza A(H1N1) Viruses
Bibliographic record
Abstract
BACKGROUND: The viral fitness of neuraminidase inhibitor (NAI)-resistant influenza viruses is believed to be impaired. Unexpectedly, an oseltamivir-resistant A(H1N1) variant containing the H274Y neuraminidase (NA) mutation recently disseminated worldwide, suggesting that the replication and virulence properties of this mutant virus were not compromised. METHODS: In vitro replicative capacities were determined for old (A/WSN/33, A/Mississipi/3/01, A/New Caledonia/20/99, and A/Solomon Islands/03/06) and recent (A/Brisbane/59/2007-like) influenza A(H1N1) viruses either harboring or not harboring the H274Y NA mutation. Ferrets were infected with the A/Brisbane/59/2007-like wild-type (WT) isolate and its H274Y NA variant. RESULTS: Old A(H1N1) WT viruses grew at higher titers than did the A/Brisbane/59/2007-like viruses in vitro. The H274Y mutation was associated with reduced viral plaque areas in cells infected with A/WSN/33 and A/Mississippi/3/01, whereas the 2 A/Brisbane/59/2007-like isolates showed similar plaque sizes. In ferrets, the pyrexic response induced by the A/Brisbane/59/2007-like H274Y mutant was significantly higher than that induced by the WT isolate. Nasal wash viral titers were significantly greater for the mutant isolate on day 2 after inoculation, whereas the 2 viruses showed similar titers between days 3 and 7 after inoculation. CONCLUSIONS: The viral fitness of the recent A/Brisbane/59/2007-like H274Y variant is not impaired, consistent with its global dissemination. These results reinforce the need for new antiviral strategies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".