1098. How Morbilliviruses Antagonize Innate Immunity and Swiftly Inactivate the Adaptive Immune System
Notice bibliographique
Résumé
INTRODUCTION. About 700,000 children die each year due to the consequences of measles-induced immunosuppression. The lack of a small animal model has limited studies of measles virus (MV) pathogenesis, but experimental infections of ferrets with canine distemper virus (CDV) recapitulate many immunosuppression hallmarks observed after MV infection: depression of tuberculin/DTH test responses, lowered leukocyte counts and antibody titers, and reduced in vitro lymphocyte proliferation activity. RESULTS. To analyze the viral determinants of immunosuppression we generated CDV either selectively receptor-blind or incapable of expressing either one, or both, candidate interferon antagonists proteins. Our analysis revealed striking similarities between the early phases of immunosuppression induced by morbilliviruses and HIV. A few days after inoculation, massive infection of primary and secondary lymphatic organs including intestinal Peyer's patches occurred depending on recognition of the signaling lymphocytic activation molecule (SLAM, CD150). Infection of about half the circulating lymphocytes, selective depletion of T-cells, and complete inhibition of the cytokine response followed. These events depend on V, the essential interferon antagonist and cytokine response inhibitor. An effect of the other viral protein C on the severity of rash and digestive symptoms was observed only in a V-defective genetic background. DISCUSSION. These findings reform our understanding of morbillivirus immunosuppression: we prove formally that SLAM is the primary morbillivirus receptor, that V is the essential interferon antagonist and cytokine response inhibitor, and that V is an infectivity factor. Understanding of the viral determinants of immunosuppression provides guidance for the development of measles virus-based multivalent vaccines and oncolytic vectors. INTRODUCTION. About 700,000 children die each year due to the consequences of measles-induced immunosuppression. The lack of a small animal model has limited studies of measles virus (MV) pathogenesis, but experimental infections of ferrets with canine distemper virus (CDV) recapitulate many immunosuppression hallmarks observed after MV infection: depression of tuberculin/DTH test responses, lowered leukocyte counts and antibody titers, and reduced in vitro lymphocyte proliferation activity. RESULTS. To analyze the viral determinants of immunosuppression we generated CDV either selectively receptor-blind or incapable of expressing either one, or both, candidate interferon antagonists proteins. Our analysis revealed striking similarities between the early phases of immunosuppression induced by morbilliviruses and HIV. A few days after inoculation, massive infection of primary and secondary lymphatic organs including intestinal Peyer's patches occurred depending on recognition of the signaling lymphocytic activation molecule (SLAM, CD150). Infection of about half the circulating lymphocytes, selective depletion of T-cells, and complete inhibition of the cytokine response followed. These events depend on V, the essential interferon antagonist and cytokine response inhibitor. An effect of the other viral protein C on the severity of rash and digestive symptoms was observed only in a V-defective genetic background. DISCUSSION. These findings reform our understanding of morbillivirus immunosuppression: we prove formally that SLAM is the primary morbillivirus receptor, that V is the essential interferon antagonist and cytokine response inhibitor, and that V is an infectivity factor. Understanding of the viral determinants of immunosuppression provides guidance for the development of measles virus-based multivalent vaccines and oncolytic vectors.
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 ».