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mutagenesis-mediated decrease of pathogenicity as a feature of the mutant spectrum of a viral populationmutagenesis-mediated减少致病性病毒的突变谱的特征
Mutagenesis-Mediated Decrease of Pathogenicity as a Feature of the Mutant Spectrum of a Viral Population 1,2¤ ´ 1 ´ 1 Marta Sanz-Ramos , Teresa Rodrıguez-Calvo , Noemı Sevilla * ´ ´ ´ 1 Centro de Investigacion en Sanidad Animal, Instituto Nacional de Investigacion y Tecnologıa Agraria y Alimentaria (CISA-INIA), Valdeolmos, Madrid, Spain, 2 Centro de ´ ´ Biologıa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientıficas, Campus de Cantoblanco, Madrid, Spain Abstract Background: RNA virus populations are heterogeneous ensembles of closely related genomes termed quasispecies. This highly complex distribution of variants confers important properties to RNA viruses and influences their pathogenic behavior. It has been hypothesized that increased mutagenesis of viral populations, by treatment with mutagenic agents, can induce alterations in the pathogenic potential of a virus population. In this work we investigate whether mutagenized foot-and-mouth disease virus (FMDV) populations display changes in their virulence in mice. Methodology and Principal Findings: FMDV C-S8c1 was passaged in BHK cells in the presence of the mutagenic agent ribavirin. Decline in viral titer and viral RNA progeny was observed in the first passage, fluctuating around a constant value thereafter. Hence, the specific infectivity remained stable during the passages. The viral population harvested from passage 9 (P9 R) showed decreased virulence in mice, with a lethal dose 50 (LD
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