Molecular Determinants of Species-Specific Interactions Between Protein Kinase R and Poxvirus K3 Orthologs
Bibliographic record
Abstract
Protein kinase R (PKR) is an antiviral protein that is involved in molecular "arms races" with viral antagonists. As a result, some PKR inhibitors, including the vaccinia virus (VACV) protein K3 and its orthologs from other poxviruses only inhibit PKRs of selected species. We previously reported contrasting inhibition patterns of human, sheep, and cow PKRs by VACV K3 and the sheeppox virus (SPPV) K3 ortholog, SPPV 011. Here we show that the differential sensitivities of cow and sheep PKRs to VACV K3 were mediated by only two residues in PKR helix αG. In contrast, SPPV 011 sensitivities were governed by additional residues and regions. Analysis of the PKR sensitivities from 20 mammalian species to VACV K3 and SPPV 011 revealed four different sensitivity patterns: some PKRs were inhibited by only one K3 ortholog, as previously reported, whereas other PKRs were either resistant or sensitive to both inhibitors. Furthermore, we characterized a residue (K45) in VACV K3 that is involved in the species-specific inhibition of PKR. Mutating this residue increased the inhibition of sheep but not human PKR, whereas it decreased the inhibition of mouse PKR, highlighting that a single mutation in a viral protein can result in distinct species-dependent inhibition changes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".