Persistence Of Dengue Virus In Stored Platelets and Red Blood Cells
Notice bibliographique
Résumé
Abstract Dengue virus (DENV), a single stranded RNA member of the Flavivirus family, is responsible for morbidity and mortality, causes ∼50 million infections annually, exists at a relatively high asymptomatic number in blood and is transfusion-transmitted. It is therefore a significant risk to blood systems globally. Universal pathogen inactivation (PI) of platelets and plasma promises to eventually eradicate DENV from blood systems, however, approval of PI in North America has been complicated as some patients may develop respiratory distress and clinical efficacy is currently being further evaluated. Moreover, the technology for PI red cells and whole blood is only in early development with a phase III clinical trial underway. While these studies will ultimately protect the blood system, it is currently unknown whether DENV can maintain its viability or even replicate under the various conditions of stored cellular blood products. Therefore, we investigated the persistence of DENV in platelet (PC) and red blood cell concentrates (RCC) throughout storage under standard blood bank conditions. Purified DENV particles (serotypes 1-4), were produced by sucrose gradient ultracentrifugation of infected Vero cell supernatants. To mimic the approximate DENV concentration known to circulate at an asymptomatic level, purified virus at 105 plaque forming units/ml was spiked into donor-derived, leukoreduced PC or RCC obtained under institutionally approved informed consent and produced by Canadian Blood Services standard operating procedures at the Network Centre for Applied Development. All units were free of bacterial contamination after production as determined by the BacT/Alert microbial detection system. Following inoculation, the PCs were stored for up to 7 days on an industry-approved rocker at 22oC, while RCC were stored for 42 days at 1-6oC. Platelet and RBC were sampled antiseptically daily or weekly (respectively) through side couplers added to the product bags. Each DENV serotype was detected using cytolytic plaque assays immediately following inoculation of platelets or RBC demonstrating the presence of infectious virus. However, possibly due to the 22oC storage conditions, viable DENV underwent logarithmic inactivation in platelet units by Day 1 post inoculation. Nevertheless, between 1-5% of the initial infectious DENV added was detected up to Day 7. This was in contrast to purified DENV in the absence of cells, suggesting virus replication in or protection by the donor platelets. The presence of DENV1-4 was confirmed by quantitative rtPCR, which showed that the DENV RNA genome was replicated with a peak at Day 3 by as much as 7-fold, with continued detection throughout the 7 day platelet storage period. These observations are consistent with platelets having known translational machinery to produce protein from mRNA. Analysis of the RBCs by plaque assays showed viable DENV throughout the 42 day storage period, consistent with stabilization of the virus at 1-6oC. Interestingly, even though RBCs do not have the ability to translate mRNA, evidence of virus replication was observed, possibly due to the presence of residual white blood cells in the leukoreduced RBC products. The possibility that Dengue viruses or other RNA viruses may persist and replicate in cellular blood products highlights the need to hasten the development and implementation of universal pathogen inactivation. Disclosures: No relevant conflicts of interest to declare.
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 | 0,001 |
| 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 | 0,001 | 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) | 0,001 | 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 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 ».