Comparative biochemical analysis of wildtype and drug resistant HIV-1 integrase subtypes B and C
Bibliographic record
Abstract
Subtype specific differences in the development of drug resistance mutations have been reported for reverse transcriptase and protease. Therefore, it is also important to compare the enzymatic activities of purified HIV-1 integrase (IN) from subtypes B and C in the wildtype (wt) enzymes, as well as those containing drug resistance mutations. We now report on the enzymatic activities of both wt IN enzymes and those containing either the E92Q or N155H mutations or both mutations together. To evaluate the enzymatic activities from non-B subtypes we cloned subtype C IN from pINDIE-C1 into a prokaryotic protein expression vector, inserted solubility mutations, described previously for subtype B IN, and resistance mutations utilizing site-directed mutagenesis. We then expressed and purified the relevant proteins. The catalytic activities of both wt enzymes were analyzed through biochemical assays for 3' processing and strand transfer (3' P and ST respectively). An extensive biochemical characterization of all purified integrase enzymes was performed, both in the presence and absence of IN inhibitors (Raltegravir, Elvitegravir and MK-2048). Our results indicate that the enzymatic activities of wt subtype B and C integrases are not significantly different, suggesting that there is little variation between subtypes B and C in regard to integrase function. In addition, wt enzymes of both subtypes displayed similar sensitivity to the IN inhibitors. The double mutant E92Q/N155H enzymes showed higher resistance to IN inhibitors than did enzymes containing only single mutations, and differences between mutated enzymes of subtype B versus C origin in regard to levels of resistance were demonstrable but not pronounced. This is the first report on the enzymatic activity of both wt and drug resistant subtype C IN enzymes. IN from subtypes B and C behave similarly in biochemical assays and in regard to susceptibility to IN inhibitors.
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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".