Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence

Enhanced mutagenesis may result in RNA virus extinction, but the molecular events underlying this process are not well understood. Here we show that 5-fluorouracil (FU)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (LCMV) resulted in preextinction populations whose consens...

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Detalles Bibliográficos
Autores: Grande-Pérez, Ana, Gómez-Mariano, Gema, Lowenstein, Pedro R., Domingo, Esteban
Tipo de recurso: artículo
Fecha de publicación:2005
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/8392
Acceso en línea:http://hdl.handle.net/10261/8392
Access Level:acceso abierto
Palabra clave:Lymphocytic choriomeningitis virus
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spelling Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequenceGrande-Pérez, AnaGómez-Mariano, GemaLowenstein, Pedro R.Domingo, EstebanLymphocytic choriomeningitis virusEnhanced mutagenesis may result in RNA virus extinction, but the molecular events underlying this process are not well understood. Here we show that 5-fluorouracil (FU)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (LCMV) resulted in preextinction populations whose consensus genomic nucleotide sequence remained unaltered. Furthermore, fitness recovery passages in the absence of FU, or alternate virus passages in the presence and absence of FU, led to profound differences in the capacity of LCMV to produce progeny, without modification of the consensus genomic sequence. Molecular genetic analysis failed to produce evidence of hypermutated LCMV genomes. The results suggest that low-level mutagenesis to enrich the viral population with defector, interfering genomes harboring limited numbers of mutations may mediate the loss of infectivity that accompanies viral extinctionThis work was supported by grants BMC 2001-1823-C02-01 and CAM 08.2/0015/2001.1 and by Fundación R. Areces. A.G.-P. was supported by a postdoctoral contract from CAM and a RyC contract from MCyTPeer reviewedAmerican Society for MicrobiologyFundación Ramón ArecesComunidad de MadridMinisterio de Ciencia y Tecnología (España)200820082005info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501178239 bytesapplication/pdfhttp://hdl.handle.net/10261/8392reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1128/JVI.79.16.10451-10459.2005info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/83922026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
title Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
spellingShingle Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
Grande-Pérez, Ana
Lymphocytic choriomeningitis virus
title_short Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
title_full Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
title_fullStr Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
title_full_unstemmed Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
title_sort Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
dc.creator.none.fl_str_mv Grande-Pérez, Ana
Gómez-Mariano, Gema
Lowenstein, Pedro R.
Domingo, Esteban
author Grande-Pérez, Ana
author_facet Grande-Pérez, Ana
Gómez-Mariano, Gema
Lowenstein, Pedro R.
Domingo, Esteban
author_role author
author2 Gómez-Mariano, Gema
Lowenstein, Pedro R.
Domingo, Esteban
author2_role author
author
author
dc.contributor.none.fl_str_mv Fundación Ramón Areces
Comunidad de Madrid
Ministerio de Ciencia y Tecnología (España)
dc.subject.none.fl_str_mv Lymphocytic choriomeningitis virus
topic Lymphocytic choriomeningitis virus
description Enhanced mutagenesis may result in RNA virus extinction, but the molecular events underlying this process are not well understood. Here we show that 5-fluorouracil (FU)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (LCMV) resulted in preextinction populations whose consensus genomic nucleotide sequence remained unaltered. Furthermore, fitness recovery passages in the absence of FU, or alternate virus passages in the presence and absence of FU, led to profound differences in the capacity of LCMV to produce progeny, without modification of the consensus genomic sequence. Molecular genetic analysis failed to produce evidence of hypermutated LCMV genomes. The results suggest that low-level mutagenesis to enrich the viral population with defector, interfering genomes harboring limited numbers of mutations may mediate the loss of infectivity that accompanies viral extinction
publishDate 2005
dc.date.none.fl_str_mv 2005
2008
2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/8392
url http://hdl.handle.net/10261/8392
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1128/JVI.79.16.10451-10459.2005
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 178239 bytes
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dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
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reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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