Inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic DNA polymers.
Virology
; 372(1): 107-17, 2008 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-18022208
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Internalização do Vírus
/
Oligonucleotídeos Fosforotioatos
/
Vírus da Coriomeningite Linfocítica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Virology
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos