English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/24845

Potential Benefits of Sequential Inhibitor-Mutagen Treatments of RNA Virus Infections

AutorPerales, Celia; Agudo, Rubén; Tejero, Héctor; Manrubia Cuevas, Susanna; Domingo, Esteban
Palabras claveFoot-and-mouth disease virus (FMDV)
Antiviral inhibitor guanidine (GU)
Fecha de publicación13-nov-2009
EditorPublic Library of Science
CitaciónPLoS Pathogens 5(11): e1000658
ResumenLethal mutagenesis is an antiviral strategy consisting of virus extinction associated with enhanced mutagenesis. The use of non-mutagenic antiviral inhibitors has faced the problem of selection of inhibitor-resistant virus mutants. Quasispecies dynamics predicts, and clinical results have confirmed, that combination therapy has an advantage over monotherapy to delay or prevent selection of inhibitor-escape mutants. Using ribavirin-mediated mutagenesis of foot-and-mouth disease virus (FMDV), here we show that, contrary to expectations, sequential administration of the antiviral inhibitor guanidine (GU) first, followed by ribavirin, is more effective than combination therapy with the two drugs, or than either drug used individually. Coelectroporation experiments suggest that limited inhibition of replication of interfering mutants by GU may contribute to the benefits of the sequential treatment. In lethal mutagenesis, a sequential inhibitor-mutagen treatment can be more effective than the corresponding combination treatment to drive a virus towards extinction. Such an advantage is also supported by a theoretical model for the evolution of a viral population under the action of increased mutagenesis in the presence of an inhibitor of viral replication. The model suggests that benefits of the sequential treatment are due to the involvement of a mutagenic agent, and to competition for susceptible cells exerted by the mutant spectrum. The results may impact lethal mutagenesis-based protocols, as well as current antiviral therapies involving ribavirin.
Versión del editorhttp://dx.doi.org/10.1371/journal.ppat.1000658
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
EDomingo_PlosPath_1000658.pdf624,99 kBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.