Macrophages differentiation confers resistance to HIV-Vpr induced apoptosis (110.10)
Bibliographic record
Abstract
Abstract Macrophages represent major viral reservoirs during HIV infection, because they are long lived and resistant to HIV cytopathic effects. We have evaluated the role of Bcl2 and IAPs (inhibitors of apoptosis), the main families of antiapoptotic proteins, in macrophage resistance during HIV infection by using the HIV accessory protein Vpr as a study model for apoptosis. Our results show that human monocytes are sensitive to Vpr but develop resistance following differentiation into macrophages. Vpr efficiently down-regulated cIAP1 and Bcl2 in sensitive monocytes but not in macrophages, suggesting that these molecules could be implicated in the enhanced resistance of macrophages to HIV-Vpr apoptosis. However, Bcl2 inactivation with the HA14-1 inhibitor was able to induce cell death on its own, with no impact on susceptibility to Vpr apoptosis. By using siRNA to knock down the expression of IAP1 and IAP2 proteins and SMAC mimetic to induce their degradation, macrophages could be sensitized to Vpr-induced cell death. Our results suggest that IAPs and not Bcl2 family confer a resistant phenotype that is relevant for macrophage survival in the context of HIV infection. Modulation of the apoptotic pathway during monocyte differentiation provides insight into the possible mechanisms for viral reservoirs persistence in macrophages and into potential therapeutic approaches to target antiapoptotic genes.
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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) | 0.002 | 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".