Dramatic caspase-dependent apoptosis in antibody-enhanced dengue virus infection of human mast cells
Bibliographic record
Abstract
Severe forms of dengue virus disease, known as dengue hemorrhagic fever and dengue shock syndrome, result from an aberrant immune response involving antibody-dependent enhancement of infection, thrombocytopenia, and a loss of vascular integrity, culminating in hemorrhage, shock, and in some cases, death. Several studies have indicated that dengue virus infection results in the induction of apoptosis of certain cells believed to be contributory players in dengue pathogenesis. However, none have specifically examined the role of antibody enhancement in the context of induction of apoptosis. Here, we show that antibody-enhanced dengue virus infection of the FcR-bearing mast cell/basophil KU812 cell line results in a massive induction of apoptosis. Confocal microscopy and flow cytometry indicate two distinct subpopulations consisting of productively infected cells and apoptotic-uninfected bystanders. Apoptosis was found to be caspase-dependent, involving global caspase activation and cleavage of poly-ADP-ribose polymerase (PARP) and D4-guanosine diphosphate dissociation inhibitor (D4-GDI). Additional FcR-bearing cells, including K562, U937, and human mast cell 1 (HMC-1), were analyzed for apoptosis induction following infection. Although all cells displayed high susceptibility to antibody-enhanced dengue virus infection, only cells of a mast cell phenotype (KU812 and HMC-1) were found to undergo apoptosis. Dengue-induced apoptosis of KU812 cells was shown to require antibody-enhanced dengue virus infection by blockade of FcgammaRII. Transfection of KU812 cells with L-SIGN/DC-SIGNR was able to overcome the requirement for antibody enhancement with regard to dengue virus infection and apoptosis.
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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".