Resistance to Apoptosis: Mechanism for the Development of HIV Reservoirs
Bibliographic record
Abstract
New insights into the physiological cell death program in mammalian cells have further confounded the central issue of T lymphocyte destruction during HIV infection. Although infected and uninfected cells die following infection, recent evidence indicates that infected and uninfected cells may have unique pathways controlling death. Two widely accepted models for apoptosis have been described, namely the intrinsic and extrinsic apoptotic pathway. In the extrinsic pathway, ligation of TNF death ligands to their receptors causes oligomerization of the death receptors and recruitment of adaptor proteins typically involving caspase 8 activation. In the intrinsic pathway, apoptotic signals converge on mitochondria to cause activation and subsequent release of cytochrome c, which leads to formation of a multiprotein complex containing Apaf-1, cytochrome c, dATP and procaspase 9. Expression of HIV proteins alters these pathways resulting in enhanced levels of apoptosis. Although HIV infection results in T cell apoptosis, under some circumstances a small fraction of CD4+ T cells and macrophages do not die following infection, indicating that this may be a critical step in the development of viral reservoirs. In addition, monocyte differentiation into macrophages leads to an apoptosis resistant phenotype characterized by upregulation of antiapoptotic molecules and lower levels of proapoptotic molecules. The development of these stable antiretroviral resistant cells represents the major obstacle in achieving a complete sterile cure. However, this provides a unique opportunity to further understand the regulation of apoptosis and may facilitate novel immune based therapies aimed at modifying apoptosis in HIV disease.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.003 |
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".