Mast Cell Infection by Zika Virus and Augmentation by Pre‐existing Dengue Virus Immunity
Notice bibliographique
Résumé
As Brazil was preparing to host the 2016 Summer Olympic Games, they were also experiencing a Zika virus (ZIKV) epidemic coinciding with rising cases of microcephaly, a congenital disorder that causes severe lifelong neurological impairment. ZIKV was later confirmed as the first sexually transmitted teratogenic Flavivirus . During the epidemic, ZIKV cases were being diagnosed as mild forms of Dengue virus (DENV), another mosquito‐borne Flavivirus known for causing Dengue hemorrhagic fever (DHF). DHF is augmented by a process called antibody‐dependent enhancement (ADE), in which pre‐existing DENV immunity can render an individual more susceptible to a subsequent DENV exposure. Based on structural similarities between ZIKV and DENV surface proteins, emerging evidence suggests anti‐DENV antibodies can cross‐react with ZIKV at non‐neutralizing levels characteristic of ADE. Therefore, a pre‐existing DENV immunity may enhance ZIKV infection and could explain the severe ZIKV manifestations in Brazil. Sentinel cells positioned in the periphery that detect infection are integral in coordinating early immune defenses. Among these immune cells, the mast cell (MC) is uniquely positioned in the intradermal space, the first point of contact between the host and an infected mosquito. MC responses to virus can be modelled in vitro, including via use of the well‐characterized KU812 cell line which express surface proteins that may be exploited by ZIKV and DENV. In particular, Fcγ receptors (FcγR), which can bind to anti‐DENV IgG antibodies that cross‐react with ZIKV can facilitate ADE. However, to our knowledge this mechanism has never been explored in the context of ZIKV‐MC interactions. Here, we sought to determine if the FcγR‐bearing KU812 MC is susceptible to (1) direct ZIKV infection and (2) ZIKV infection in the presence of anti‐DENV antibodies that cross‐react with ZIKV. Cells were infected with PRVABC59‐ZIKV (MOI=1) directly or in the presence of anti‐DENV antibodies for 72 hours. Supernatants of ZIKV infected MC cultures were then harvested and virus titre quantified by plaque assay. A significant increase in viral titre (10 4 PFU/mL) was detected in MCs directly infected with ZIKV compared to MCs infected with UV‐inactivated ZIKV (0 PFU/mL). Furthermore, a significant viral titre (10 6 PFU/mL) was detected in MCs infected with ZIKV pre‐incubated with anti‐DENV antibodies when compared to MCs infected with ZIKV pre‐incubated with isotype control antibodies (10 4 PFU/mL). Additionally, significant CCL5 secretion was detected by ELISA in MCs infected in the presence of DENV antibodies compared to MCs directly infected with ZIKV, suggesting a distinct chemokine response to infection in each context. This work is the first to define ZIKV infection in a mast cell model. Additionally, we report an antigen‐specific antibody‐mediated infection of ZIKV in KU812 MCs. Therefore, MCs may be a contributor in ZIKV pathogenesis during a primary exposure and significantly augment ZIKV infection in the context of pre‐existing DENV immunity. Support or Funding Information Supported by the Natural Sciences and Engineering Research council of Canada (NSERC); Canada Foundation for innovation (CFI); Government of Ontario; and, Brock University
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 | 0,000 |
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 ».