Heterologous expression of influenza hemagglutinin leads to early and transient activation of the unfolded protein response in <i>Nicotiana benthamiana</i>
Bibliographic record
Abstract
Summary The unfolded protein response (UPR) allows cells to cope with endoplasmic reticulum (ER) stress induced by the accumulation of misfolded proteins in the ER. Due to its sensitivity to Agrobacterium tumefaciens , model plant Nicotiana benthamiana is widely employed for the transient expression of recombinant proteins of biopharmaceutical interest, including therapeutic antibodies and virus surface proteins used for vaccine production. As such, study of the plant UPR is of practical significance, since enforced expression of complex secreted proteins often results in ER stress. After 6 days of expression, we recently reported that influenza hemagglutinin (HA) induces accumulation of UPR proteins. Since the upregulation of corresponding UPR genes was not detected at this time point, accumulation of UPR proteins was hypothesized to either be independent of transcriptional regulation, or associated with early but transient UPR gene upregulation. Using time course sampling, we here show that HA expression does result in early and transient activation of the UPR, as inferred from unconventional splicing of NbbZIP60 transcripts and induction of UPR genes with varied functions. The transient nature of HA-induced UPR suggests that this response was sufficient to cope with ER stress provoked by expression of the secreted protein, as opposed to an antibody that triggered a stronger and more sustained UPR. As defense-related genes were induced after the peak of UPR activation and correlated with high increase in HA protein accumulation, we hypothesize that these immune responses, rather than the UPR, were responsible for the onset of necrotic symptoms on HA-expressing leaves. One-sentence summary Agrobacterium -mediated expression of influenza hemagglutinin results in early and transient activation of the unfolded protein response, preventing deleterious effects caused by unresolved endoplasmic reticulum stress.
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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 | 0.000 | 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) | 0.000 | 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".