Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner.

Détails

ID Serval
serval:BIB_3DBCC46816C6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner.
Périodique
Cell Host and Microbe
Auteur(s)
Popkin D.L., Teijaro J.R., Sullivan B.M., Urata S., Rutschmann S., de la Torre J.C., Kunz S., Beutler B., Oldstone M.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Statut éditorial
Publié
Date de publication
2011
Volume
9
Numéro
3
Pages
212-222
Langue
anglais
Résumé
The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), which naturally persists in rodents, represents a model for HIV, HBV, and HCV. Cleavage of the viral glycoprotein precursor by membrane-bound transcription factor peptidase, site 1 (Mbtps1 or site-1 protease), is crucial for the life cycle of arenaviruses and therefore represents a potential target for therapy. Recently, we reported a viable hypomorphic allele of Mbtps1 (woodrat) encoding a protease with diminished enzymatic activity. Using the woodrat allele, we examine the role of Mbtps1 during persistent LCMV infection. Surprisingly, Mbtps1 inhibition limits persistent but not acute viral infection and is associated with an organ/cell type-specific decrease in viral titers. Analysis of bone marrow-derived dendritic cells from woodrat mice supports their specific role in resolving persistent viral infection. These results support in vivo targeting of Mbtps1 in the treatment of arenavirus infections and demonstrate a critical role for dendritic cells in persistent viral infections.
Mots-clé
Animals, Animals, Genetically Modified/immunology, Animals, Genetically Modified/virology, Antigens, Viral/metabolism, Arenaviridae Infections/immunology, Arenaviridae Infections/virology, B-Lymphocytes/immunology, Bone Marrow Cells/immunology, Bone Marrow Cells/virology, Dendritic Cells/immunology, Immunity, Innate, Immunocompromised Host, Kidney/immunology, Kidney/virology, Liver/immunology, Liver/virology, Lymphocytic choriomeningitis virus/growth & development, Lymphocytic choriomeningitis virus/physiology, Mice, Mice, Inbred C57BL, Mutation, Proprotein Convertases/genetics, Proprotein Convertases/immunology, Serine Endopeptidases/genetics, Serine Endopeptidases/immunology, Spleen/immunology, Spleen/virology, T-Lymphocytes/immunology, Viral Plaque Assay, Viral Tropism
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/04/2013 18:02
Dernière modification de la notice
20/08/2019 14:34
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