Lymphocytes Can Play The Trojan-Horse Role in Polyoma BKV Infection.
Bibliographic record
Abstract
BKV nephropathy (BKN) is currently the leading cause of early renal allograft loss. The process starts after immune suppression following renal transplantation, which causes BK virus (BKV) reactivation, resulting in lytic injury of renal tubular epithelial cells followed by tubular inflammation, and allograft destruction. Although the role played by lymphocytes in BKN pathogenesis remains largely uncharacterized, both cellular and humoral immunity were demonstrated to be involved in BKV early elimination. Our laboratory is interested in characterizing the role played by lymphocytes in BKV pathogenesis. Using real-time polymerase chain reaction (rt-PCR) and immunoblotting, we demonstrated that BKV can infect human B and T cell lines. BKV was also shown to infect and replicate in primary lymphocytes from peripheral blood at higher efficiency than cell lines. Viral replication was associated with remarkable changes in cell shape and behaviour, with cells acquiring a refractile, fusiform appearance and becoming more adhesive. B lymphocytes infected with BKV differentiated into both memory and plasma cells, but a significant proportion of these differentiated cells were not specific for BKV proteins. These observations may provide a clue into the accumulation of plasma cells in renal transplants affected by BK nephropathy. The potential transmission of BKV virions between immune lymphocytes was confirmed by rt-PCR of CFSE-labelled BKV infected and non-infected purified lymphocytes that were previously incubated and sorted using flow cytometry. To examine the mechanism of viral transmission, we used fluorescent microscopy to image lymphocytes from PBMCs infected with BKV in vitro. Using a monoclonal antibody against VP1 capsid protein, we found that BKV induced lymphocytes to form long tiny tubules (tunneling nanotubules, TNT) that transmitted both BKV virions and large T-antigen between neighbouring cells. BKV was also transmitted between adjacent lymphocytes through direct cell-to-cell transfer. Viral transmission between lymphocytes might elucidate a viral escape mechanism that evades the host humoral immunity. Other mechanisms of viral transmission are still under investigation. This project is anticipated to establish a baseline for understanding host-viral interaction in patients with BKN, which could also help in designing tools for assessment of, and following up progression of BKN in allograft recipients. DISCLOSURES:Tibbles, L.: Grant/Research Support, Pfizer Canada, Investigator Initiated Research Grant, Other, Pfizer Canada, Support for monitoring randomized clinical trial.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".