Bacterial DNA Protects Monocytic Cells against HIV-Vpr–Induced Mitochondrial Membrane Depolarization
Bibliographic record
Abstract
Monocytes and macrophages are important HIV reservoirs, as they exhibit marked resistance to apoptosis upon infection. However, the mechanism underlying resistance to apoptosis in these cells is poorly understood. Using HIV-viral protein R-52-96 aa peptide (Vpr), we show that primary monocytes and THP-1 cells treated with Vpr are highly susceptible to mitochondrial depolarization, but develop resistance following stimulation with bacterial DNA or CpG oligodeoxynucleotide. We have shown that Vpr-induced mitochondrial depolarization is mediated by TNFR-associated factor-1 (TRAF-1) and TRAF-2 degradation and subsequent activation of caspase-8, Bid, and Bax. To provide the mechanism governing such resistance to mitochondrial depolarization, our results show that prior stimulation with CpG oligodeoxynucleotide or Escherichia coli DNA prevented: 1) TRAF-1/2 downregulation; 2) activation of caspase-8, Bid, and Bax; and 3) subsequent mitochondrial depolarization and release of apoptosis-inducing factor and cytochrome c Furthermore, this protection was mediated by upregulation of antiapoptotic protein (c-IAP-2) through calmodulin-dependent kinase-II activation. Thus, c-IAP-2 may prevent Vpr-mediated mitochondrial depolarization through stabilizing TRAF-1/2 expression and sequential inhibition of caspase-8, Bid, and Bax.
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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".