Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers.

Details

Serval ID
serval:BIB_B324D6E53D2B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers.
Journal
Virology
Author(s)
Lee A.M., Rojek J.M., Gundersen A., Ströher U., Juteau J.M., Vaillant A., Kunz S.
ISSN
0042-6822 (Print)
ISSN-L
0042-6822
Publication state
Published
Issued date
2008
Volume
372
Number
1
Pages
107-117
Language
english
Abstract
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.
Keywords
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
Yes
Create date
17/04/2013 11:56
Last modification date
20/08/2019 15:21
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