Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression.

Détails

ID Serval
serval:BIB_DA6219E72AE7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Bergthaler A., Flatz L., Hegazy A.N., Johnson S., Horvath E., Löhning M., Pinschewer D.D.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2010
Volume
107
Numéro
50
Pages
21641-21646
Langue
anglais
Résumé
The Clone 13 (Cl13) strain of lymphocytic choriomeningitis virus is widely studied as a model of chronic systemic viral infection. Here, we used reverse genetic techniques to identify the molecular basis of Cl13 persistence and immunosuppression, the characteristics differentiating it from the closely related Armstrong strain. We found that a single-point mutation in the Cl13 polymerase was necessary and partially sufficient for viral persistence and immunosuppression. A glycoprotein mutation known to enhance dendritic cell targeting accentuated both characteristics but when introduced alone, failed to alter the phenotype of the Armstrong strain. The decisive polymerase mutation increased intracellular viral RNA load in plasmacytoid dendritic cells, which we identified as a main initial target cell type in vivo, and increased viremia in the early phase of infection. These findings establish the enhanced replicative capacity as the primary determinant of the Cl13 phenotype. Viral persistence and immunosuppression can, thus, represent a direct consequence of excessive viral replication overwhelming the host's antiviral defense.
Mots-clé
Animals, CD8-Positive T-Lymphocytes/immunology, Genome, Viral, Immunosuppression, Lymphocytic choriomeningitis virus/genetics, Lymphocytic choriomeningitis virus/immunology, Mice, Mice, Inbred C57BL, Point Mutation, Viral Proteins/genetics, Viral Proteins/metabolism, Viremia, Virus Replication
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/03/2012 19:14
Dernière modification de la notice
09/05/2019 2:04
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