The Role of the Early Secretory Pathway in Foot-and-Mouth Disease Virus Replication
Bibliographic record
Abstract
Foot-and-Mouth Disease Virus (FMDV) induces rearrangements of host-cell membranes to generate vesicles that are believed to provide platforms for formation of the viral replication complex. The cellular origin of these vesicles and the properties that make them favourable for replication are poorly understood. For some Picornaviruses these vesicles are thought to derive from membranes of the secretory pathway. In this thesis, I have investigated a role for membranes of the secretory pathway in FMDV infection. Key cellular proteins involved in regulating the flow of membranes through the secretory pathway between the ER and Golgi were inhibited using expression of dominant-negative (dn) proteins and small interfering RNA (siRNA) and the effect on FMDV infection determined. Inhibition of ER export using a drug (H89) or Sar1 (the GTPase required for COPII transport vesicle formation at ER exit sites) reduced FMDV infection. In contrast, stabilisation of COPII coats, or inhibition of Arf1 or Rab proteins, that are involved in the secretory pathway after the formation of COPII vesicles, had little or no inhibitory effect on infection. Interestingly inhibition of Arf1, Rab1 or Rab2 enhanced infection. In contrast, Arf1 reduced infection by bovine enterovirus which is inhibited by Brefeldin-A, and therefore likely to be dependent on Arf1 for replication. These results show that Sar1 and/or COPII vesicle formation is necessary for FMDV infection and that inhibiting the formation of COPI coats is in some way advantageous to FMDV infection. These results suggest that FMDV targets COPII vesicles membranes before the COPII/COPI exchange and facilitates FMDV infection and that COPI components are not required.
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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 | 0.001 | 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".