Mapping of Genetic Determinants of Rubella Virus Associated with Growth in Joint Tissue
Bibliographic record
Abstract
Rubella virus (RV) strains vary in their abilities to replicate and persist in cell cultures derived from human joint tissue (synovial cells [SC]), and this arthrotropism appears to be linked to their association with joint symptoms in vivo. In order to map the genetic determinants of arthrotropism, an infectious clone of the Cendehill vaccine strain of RV was constructed, as well as two chimeric clones containing cDNAs from both Cendehill and Therien (wild-type) strains. Replacement of the entire structural gene region of Therien in the infectious clone pROBO302 with the corresponding region of Cendehill did not affect growth in SC. A further observation that Cendehill bound equally well to SC and the permissive Vero cell line indicated that restriction was not at the level of receptor binding, a function of the envelope proteins. Mutations that affected growth in joint cells were mapped to two locations in the nonstructural gene region. The first of these (nucleotides 2803 and 6416) resulted in a 10-fold decrease in yield of progeny virus from SC. This region contained five mutations, at nucleotides 2829, 3060, 3164, and 3528 (near the carboxy terminus of P150 where the protease domain is located) and at nucleotide 4350 in p90. Further substitution of the sequence representing nucleotides 1 to 2803 to give a complete Cendehill infectious clone restricted growth in SC by a further 100-fold to less than 10 PFU/ml. This region contains three mutations, at nucleotides 34, 37, and 55, within the 5' stem-loop structure. In conclusion, the Cendehill-specific mutations believed to be determinants of joint cell growth are located in two regions, the 5' nontranslated region and in a sequence that encodes the carboxy-terminal region of p150 extending into the helicase domain of p90.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".