Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers.
Détails
ID Serval
serval:BIB_B324D6E53D2B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers.
Périodique
Virology
ISSN
0042-6822 (Print)
ISSN-L
0042-6822
Statut éditorial
Publié
Date de publication
2008
Volume
372
Numéro
1
Pages
107-117
Langue
anglais
Résumé
The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) represents a powerful experimental model for the study of the basic virology and pathogenesis of arenaviruses. In the present study, we used the LCMV model to evaluate the anti-viral potential of phosphorothioate oligonucleotides against arenaviruses. Our findings indicate that amphipathic DNA polymers (APs) are potent inhibitors of infection with a series of LCMV isolates with IC(50) in the low nanomolar range. APs target the surface glycoprotein (GP) of LCMV and block viral entry and cell-cell propagation of the virus, without affecting later steps in replication or release of progeny virus from infected cells. The anti-viral action of APs is sequence-independent but is critically dependent on their size and hydrophobicity. Mechanistically, we provide evidence that APs disrupt the interaction between LCMVGP and its cellular receptor, alpha-dystroglycan. Exposure of LCMV to APs does not affect the stability of the GP virion spike and has no effect on the conformation of a neutralizing antibody epitope, suggesting rather subtle changes in the conformation and/or conformational dynamics of the viral GP.
Mots-clé
Animals, Antiviral Agents/pharmacology, Cell Line, Cercopithecus aethiops, Cricetinae, Dystroglycans/metabolism, Humans, Hydrophobic and Hydrophilic Interactions, Lymphocytic choriomeningitis virus/drug effects, Lymphocytic choriomeningitis virus/pathogenicity, Membrane Glycoproteins/metabolism, Phosphorothioate Oligonucleotides/pharmacology, Vero Cells, Virus Internalization/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/04/2013 12:56
Dernière modification de la notice
20/08/2019 16:21