Reverse genetics-generated elastase-dependent swine influenza viruses are attenuated in pigs
Bibliographic record
Abstract
Influenza A virus causes significant morbidity in swine, resulting in a substantial economic burden. Swine influenza virus (SIV) infection also poses important human public health concerns. It has been shown that conversion of the haemagglutinin (HA) cleavage site from a trypsin-sensitive motif to an elastase-sensitive motif resulted in attenuated viruses in mouse models. However, application of this attenuation approach in a natural host has not been achieved yet. Here, we report that using reverse genetics, we generated two mutant SIVs derived from strain A/SW/SK/18789/02 (H1N1). Mutant A/SW/SK-R345V carries a mutation from arginine to valine at aa 345 of HA. Similarly, mutant A/SW/SK-R345A encodes alanine instead of arginine at aa 345 of HA. Our data showed that both mutants are solely dependent on neutrophil elastase cleavage in tissue culture. These tissue culture-grown mutant SIVs showed similar growth properties in terms of plaque size and growth kinetics to the wild-type virus. In addition, SIV mutants were able to maintain their genetic information after multiple passaging on MDCK cells. Furthermore, mutant SIVs were highly attenuated in pigs. Thus, these mutants may have the potential to serve as live attenuated vaccines.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".