ADP-ribosyl–binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication
Bibliographic record
Abstract
Significance Alphaviruses are mosquito-borne RNA viruses that cause encephalitis, rash, and arthritis. Alphavirus nonstructural protein 3 (nsP3) has a highly conserved macrodomain that can bind and remove ADP-ribose (ADPr) residues from ADP-ribosylated proteins, but its role in virus replication was not known. We show that alphavirus replication in neural cells depends on protein ADP ribosylation and that nsP3s with mutations that eliminate ADPr binding cannot form a functional replicase. Mutations that decrease ADPr binding result in fewer infected cells, while mutations that increase binding but decrease hydrolase activity infect cells normally but amplify replication complexes less well. Therefore, alphavirus replication requires nsP3 macrodomain interaction with one or more ADP-ribosylated proteins, as is consistent with the observed high conservation of this region.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".