Bacterial DNA-induced anti-apoptotic c-IAP-2 protects human monocytic cells against HIV-Vpr-mediated mitochondrial membrane depolarization and apoptosis through TRAF 1/2 via sequential inhibition of pro-apoptotic Caspase 8, Bid and Bax (108.7)
Bibliographic record
Abstract
Abstract Monocytic cells are important HIV reservoirs and exhibit marked resistance to apoptosis upon infection, thereby hindering clearing of pathogens. However, the mechanism underlying the development of resistance to apoptosis in these cells is poorly understood. Using Vpr-52-96 amino acids peptide (Vpr), a HIV accessory protein, as a model for apoptosis, we have previously shown that prior treatment with CpG or E.coli DNA prevented Vpr-mediated apoptosis by induction of anti apoptotic c-IAP-2 gene via calmodulin-dependent kinase II (CAMK-II) activation in human monocytes and promonocytic THP-1 cells. Herein, we show that c-IAP-2 induced by bacterial DNA in a CaMK-II dependant manner, protects against Vpr-mediated mitochondrial depolarization. Vpr-induced mitochondrial depolarization and apoptosis is mediated by TRAF1/2 downregulation and subsequent activation of proapoptotic caspase-8, bid and bax. Treatment of cells with bacterial DNA, through c-IAP-2 induction, prevented these effects of Vpr, thereby protecting against Vpr-mediated mitochondrial depolarization and apoptosis. Overall, these results suggest a key role played by bacterial DNA-induced c-IAP-2 in preventing Vpr-mediated mitochondrial depolarization and apoptosis through prevention of TRAF 1/2 downregulation and sequential inhibition of caspase 8, bid and bax. Furthermore, strategies based on suppressing c-IAP-2 by targeting CaMK-II, TRAF1/2 or Caspase-8 may be helpful in controlling reservoir formation.
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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 | 0.000 |
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".