Identification of a Novel Immunosubversion Mechanism Mediated by a Virologue of the B-Lymphocyte Receptor TACI
Bibliographic record
Abstract
TACI (transmembrane activator and calcium modulator and cyclophilin ligand [CAML] interactor) is a part of a novel network of ligands and receptors involved in B-cell survival and isotype switching. The TACI protein mediates its effects through CAML, an endoplasmic reticulum (ER)-localized protein that controls Ca(2+) efflux. The adenovirus E3-6.7K protein prevents inflammatory responses and also confers resistance from a variety of apoptotic stimuli and maintains ER Ca(2+) homeostasis; however, the mechanism of action is unknown. Here, we provide evidence that E3-6.7K shares sequence homology with TACI and inhibits apoptosis and ER Ca(2+) efflux through an interaction with CAML, a Ca(2+)-modulating protein. We demonstrate a direct interaction between E3-6.7K and CAML and reveal that the two proteins colocalize in an ER-like compartment. Furthermore, the interaction between the two proteins is localized to the N-terminal domain of CAML and to a 22-amino-acid region near the C terminus of E3-6.7K termed the CAML-binding domain (CBD). Mutational analysis of the CBD showed that an interaction with CAML is required for E3-6.7K to inhibit thapsigargin-induced apoptosis and ER Ca(2+) efflux. E3-6.7K appears to be the first virologue of TACI to be identified. It targets CAML in a novel immunosubversive mechanism to alter ER Ca(2+) homeostasis, which consequently inhibits inflammation and protects infected cells from 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".