Evolution of Recombinant Lymphocytic Choriomeningitis Virus/Lassa Virus In Vivo Highlights the Importance of the GPC Cytosolic Tail in Viral Fitness

Détails

ID Serval
serval:BIB_5F51A387AA42
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Evolution of Recombinant Lymphocytic Choriomeningitis Virus/Lassa Virus In Vivo Highlights the Importance of the GPC Cytosolic Tail in Viral Fitness
Périodique
Journal of Virology
Auteur(s)
Sommerstein R., Ramos da Palma J., Ölschläger S., Bergthaler A., Barba L., Lee B.P.L., Pasquato A., Flatz L.
ISSN
0022-538X (Print)
1098-5514 (Electronic)
ISSN-L
0022-538X
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
88
Numéro
15
Pages
8340-8348
Langue
anglais
Notes
Publication types: Genetic Diversity and Evolution ; research-article Identifiant PubMed Central: PMC4135970
Résumé
A key characteristic of arenaviruses is their ability to establish persistent infection in their natural host. Different factors like host age, viral dose strain, and route of infection may contribute to the establishment of persistence. However, the molecular mechanisms governing persistence are not fully understood. Here, we describe gain-of-function mutations of lymphocytic choriomeningitis virus (LCMV) expressing Lassa virus (LASV) GP, which can prolong viremia in mice depending on the sequences in the GP-2 cytoplasmic tail. The initial mutant variant (rLCMV/LASV mut GP) carried a point mutation in the cytosolic tail of the LASV glycoprotein GP corresponding to a K461G substitution. Unlike what occurred with the original rLCMV/LASV wild-type (wt) GP, infection of C57BL/6 mice with the mutated recombinant virus led to a detectable viremia of 2 weeks' duration. Further replacement of the entire sequence of the cytosolic tail from LASV to LCMV GP resulted in increased viral titers and delayed clearance of the viruses. Biosynthesis and cell surface localization of LASV wt and mut GPs were comparable.
IMPORTANCE: Starting from an emerging virus in a wild-type mouse, we engineered a panel of chimeric Lassa/lymphocytic choriomeningitis viruses. Mutants carrying a viral envelope with the cytosolic tail from the closely related mouse-adapted LCMV were able to achieve a productive viral infection lasting up to 27 days in wild-type mice. Biochemical assays showed a comparable biosynthesis and cell surface localization of LASV wt and mut GPs. These recombinant chimeric viruses could allow the study of immune responses and antivirals targeting the LASV GP.
Mots-clé
Antigens, Viral/genetics, Glycoproteins/genetics, Lassa virus/genetics, Lassa virus/growth & development, Lymphocytic choriomeningitis virus/genetics, Lymphocytic choriomeningitis virus/growth & development, Mutant Proteins/genetics, Mutant Proteins/metabolism, Protein Structure, Tertiary/genetics, Recombinant Proteins/genetics, Recombinant Proteins/metabolism, Viral Proteins/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/07/2016 11:04
Dernière modification de la notice
20/08/2019 15:17
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