Rhinovirus C infection of human airway epithelial cells causes transient replication‐dependent changes in cellular architecture and barrier function
Notice bibliographique
Résumé
RATIONALE Infections with human rhinovirus (HRV)‐C strains are associated with more severe exacerbations and increased hospitalizations in children with asthma. Although the replication cycles of HRV‐A and B strains have been extensively studied using cells of non‐airway origin (e.g. HeLa cells), HRV‐C replication within human airway epithelial cells (HAE) remains poorly understood as HRV‐C exclusively infects highly‐differentiated HAE. We have recently shown that HRV infections can be completely cleared from HAE without any requirement for immune cells. Our data suggest that mechanism of epithelial clearance involves a combination of shedding of infected cells, and antiviral responses, culminating in re‐differentiation. We are now seeking to elucidate the mechanisms by which HRV‐C remodels HAE cellular architecture during replication. We have focused on the modulation of cytoskeletal signaling pathways and resulting transient loss of barrier function. METHODS Highly differentiated air‐liquid interface (ALI) cultures of HAE, isolated from normal non‐transplanted human lungs, were infected with HRV‐C15 and monitored at 24, 48, 72, 96, 120, 144 hours post‐infection. HRV‐C15 replication kinetics were evaluated by serial apical washes every 24h to assess shed virus levels and cell lysates to quantify intracellular viral RNA by RT‐PCR. Studies of changing cytoskeletal architecture and intercellular junctions were performed using immunofluorescence staining for ZO‐1 and f‐actin. Other stimuli include replication‐deficient HRV, poly(I:C) (a mimic of the double‐stranded RNA produced during HRV replication), ROCK inhibitors, cytochalasin D (actin disruptor), and paclitaxel (microtubule stabilizer). Barrier function studies in Ussing chambers used FITC‐dextran (permeability) and measured real‐time transepithelial electrical resistance (TEER). RESULTS HRV‐C15 causes dramatic remodeling of highly‐differentiated HAE that follows the time course of viral replication and clearance from 24h to 144h. These changes include co‐localization of dsRNA‐positive cells with apically expressed ZO‐1 (indicative of infected cell shedding). Transient loss of barrier function is prominent at peak viral levels 24h post‐infection, but recovers with re‐differentiation within 144h. Preliminary data suggests that cytoskeletal inhibitors diminish the ability of HRV‐C15 to replicate and HAE shedding to occur; indicating a critical role for cytoskeletal signaling in HRV‐C15 replication. CONCLUSION We conclude that a HRV‐C serotype induces altered cellular architecture in HAE that is associated with disruption of the actin cytoskeleton and intercellular junctions. Future studies will evaluate the role of Rho GTPase signaling in HRV‐C replication or HAE shedding. Support or Funding Information This study was supported by grant number PJT‐159635 from the Canadian Institutes of Health Research (CIHR). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».