The SARS-CoV-2 nonstructural protein 15 collapses the host cytoskeleton by interacting with the host keratin type II cytoskeletal 1
Bibliographic record
Abstract
Abstract COVID-19, the deadliest recorded pandemic of the 21 st century, was caused by a novel coronavirus, SARS-CoV-2. To explore why this coronavirus was significantly more pathogenic than its predecessors, more information is needed about the functions of the viral proteins that contributed to this uptick in virulence. This study explored how one of these viral proteins, the nonstructural protein 15 (NSP15), interacts with the host. Our findings revealed a novel protein-protein interaction between NSP15 and the host keratin type II cytoskeletal 1 in Vero E6 cells, as determined by mass spectrometry, and subsequently validated by immunoprecipitation. We observed that when NSP15 was delivered into Vero E6 cells, the fibrous network of keratin intermediate filaments was disrupted, and the nuclear structure was lost. This disruption of the keratin cytoskeleton was then shown to cause a statistically significant reduction in cell viability of Vero E6 cells. These results indicate that the presence of NSP15 in host cells leads to a collapse of the keratin cytoskeleton. This cytoskeletal collapse could be a mechanism the virus employs to escape the infected host cell via cell lysis, once significant amounts of viral protein and progeny have accumulated.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".