Mapping ganciclovir resistance in the human herpesvirus‐6 U69 protein kinase
Bibliographic record
Abstract
Human herpesvirus-6 (HHV-6) is a growing concern in immunocompromised individuals, such as in the transplant setting. Alone, or in concert with human cytomegalovirus (HCMV), infections with HHV-6 are often severe enough to require antiviral therapy, generally in the form of ganciclovir (GCV). GCV resistance in HCMV is well documented, both clinically and in the laboratory, and has been shown to result from mutations in the UL97 protein kinase and/or UL54 DNA polymerase. GCV resistance in HHV-6 has been documented. However, to date, it has only been investigated to a limited extent. The baculovirus system has previously been shown to be useful in studying GCV resistance with respect to herpesvirus protein kinase mutations. Using the baculovirus system, we created recombinant baculoviruses expressing either a wild-type HHV-6 U69 protein kinase or a mutated form containing homologous mutations to those documented in the UL97 protein kinase of GCV resistant HCMV isolates. The recombinant baculoviruses were used to infect Sf-9 cells and cultured in the presence of GCV to determine the effect of the HHV-6 U69 protein kinase mutations on GCV susceptibility. Mutations in the HHV-6 U69 protein kinase, homologous to those in the HCMV UL97 protein kinase documented to cause GCV resistance, result in GCV resistance in the recombinant baculoviruses.
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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 | 0.006 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".