Lymphocytes Can Play The Trojan-Horse Role in Polyoma BKV Infection.
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».