Effects of N-linked glycosylation of the fusion protein on replication of human metapneumovirus in vitro and in mouse lungs
Bibliographic record
Abstract
The fusion (F) protein is an important membrane glycoprotein necessary for cellular entry and replication of human metapneumovirus (hMPV). Selective prevention of N-linked glycosylation may compromise the catalytic and fusion functions of the F protein. By using site-directed mutagenesis and reverse genetics, recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein were constructed. M1, which lacked glycosylation at position 57 of the F protein, had slightly compromised replication, whereas M2 and M4, which lacked glycosylation at position(s) 172 or 57 and 172, respectively, showed profound impairment of replication when compared with wild-type (WT) NL/1/00-GFP virus in both Vero E6 cells and mouse lungs. M2 was less fit than WT virus in vitro and in immunocompromised mouse lungs. The F proteins of WT and mutant viruses were similarly expressed on the infected cell membrane, while the activated fusion protein subunits, F1 of M2 and M4, were produced in lower quantities compared with those of WT and M1 virus. The mutated viruses lacking N-linked glycosylation at position 353, either individually or together with other sites, could not be recovered. Thus, N-linked glycosylation may be involved in the catalysis of the fusion protein from F0 to F1 and F2, which is critical for fusion function. Strategies targeting N-linked glycosylation may be helpful for developing attenuated live vaccines or antiviral drugs for hMPV.
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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 | 0.000 |
| 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) | 0.000 | 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".