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

Bergthaler, Andreas and Flatz, Lukas and Hegazy, Ahmed N. and Johnson, Susan and Horvath, Edit and Löhning, Max and Pinschewer, Daniel D.. (2010) Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression. Proceedings of the National Academy of Sciences of the United States of America, 107 (50). pp. 21641-21646.

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:15 Dec 2020 12:55
Deposited On:15 Dec 2020 12:55

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