English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/8283
Compartir / Impacto:
Add this article to your Mendeley library MendeleyBASE
Citado 75 veces en Web of Knowledge®  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar otros formatos: Exportar EndNote (RIS)Exportar EndNote (RIS)Exportar EndNote (RIS)

Mutagenesis versus inhibition in the efficiency of extinction of foot-and-mouth disease virus

Autor Pariente, Nonia; Airaksinen, Antero; Domingo, Esteban
Palabras clave Foot-and-mouth disease virus
Fecha de publicación 2003
EditorAmerican Society for Microbiology
Citación Journal of Virology, 2003, p. 7131-7138, Vol. 77, No. 12
ResumenRNA viruses replicate near the error threshold for maintenance of genetic information, and an increase in mutation frequency during replication may drive RNA viruses to extinction in a process termed lethal mutagenesis. This report addresses the efficiency of extinction (versus escape from extinction) of foot-and-mouth disease virus (FMDV) by combinations of the mutagenic base analog 5-fluorouracil (FU) and the antiviral inhibitors guanidine hydrochloride (G) and heparin (H). Selection of G- or H-resistant, extinction-escape mutants occurred with low-fitness virus only in the absence of FU and with high-fitness virus with some mutagen-inhibitor combinations tested. The combination of FU, G, and H prevented selection of extinction-escape mutants in all cases examined, and extinction of high-fitness FMDV could not be achieved by equivalent inhibitory activity exerted by the nonmutagenic agents. The G-resistant phenotype was mapped in nonstructural protein 2C by introducing the relevant mutations in infectious cDNA clones. Decreases in FMDV infectivity were accompanied by modest decreases in the intracellular and extracellular levels of FMDV RNA, maximal intracellular concentrations of FU triphosphate, and a decrease in the intracellular concentrations of UTP. In addition to indicating a key participation of mutagenesis in virus extinction, the results suggest that picornaviruses provide versatile experimental systems to approach the problem of extinction failure associated with inhibitor-escape mutants during treatments based on enhanced mutagenesis
Versión del editorhttp://dx.doi.org/10.1128/JVI.77.12.7131-7138.2003
URI http://hdl.handle.net/10261/8283
ISSN0022-538X (print)
1098-5514 (online)
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
NPariente_JVirol_7131.pdf287,89 kBAdobe PDFVista previa
Mostrar el registro completo

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