English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/8283
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

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

AuthorsPariente, Nonia; Airaksinen, Antero; Domingo, Esteban
KeywordsFoot-and-mouth disease virus
Issue Date2003
PublisherAmerican Society for Microbiology
CitationJournal of Virology, 2003, p. 7131-7138, Vol. 77, No. 12
AbstractRNA 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
Publisher version (URL)http://dx.doi.org/10.1128/JVI.77.12.7131-7138.2003
URIhttp://hdl.handle.net/10261/8283
DOI10.1128/JVI.77.12.7131-7138.2003
ISSN0022-538X
E-ISSN1098-5514
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
NPariente_JVirol_7131.pdf287,89 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.