Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis
Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis
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DOI：
10.1016/s0042-6822(03)00144-2
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发表时间：
2003-07-05
期刊：
影响因子：
3.7
通讯作者：
Domingo, E
中科院分区：
文献类型：
--
作者：
Airaksinen, A;Pariente, N;Domingo, E
持续感染口蹄疫病毒（FMDV）的BHK-21细胞可以通过抗病毒核苷类似物利巴韦林治疗而治愈。为了研究这一过程是否涉及病毒种群突变谱中突变数量的增加，从用利巴韦林治疗或未治疗的持续感染细胞中克隆了病毒基因组。与平行的未处理培养物相比，在处理培养物的病毒基因组中观察到与利巴韦林治疗相关的突变频率增加高达10倍。为了探讨增强诱变的可能机制，我们研究了利巴韦林与鸟苷和霉酚酸在鸟苷存在或不存在的情况下的诱变效果。测定所有处理后细胞内核苷酸浓度的变化。结果表明，增加的突变频率不是依赖于核苷酸库失衡或由于选择预先存在的基因组，而是由利巴韦林的诱变作用产生的。(C) 2003 Elsevier Science（美国）版权所有。
BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) can be cured of virus by treatment with the antiviral nucleoside analogue ribavirin. To study whether the process involved an increase in the number of mutations in the mutant spectrum of the viral population, viral genomes were cloned from persistently infected cells treated or untreated with ribavirin. An increase of up to 10-fold in mutation frequencies associated with ribavirin treatment was observed in the viral genomes from the treated cultures as compared with parallel, untreated cultures. To address the possible mechanisms of enhanced mutagenesis, we investigated the mutagenic effects of ribavirin together with guanosine, and mycophenolic acid in the presence or absence of guanosine. Changes in the intracellular nucleotide concentrations were determined for all treatments. The results suggest that the increased mutation frequencies were not dependent on nucleotide pool imbalances or due to selection of preexisting genomes but they were produced by a mutagenic action of ribavirin. (C) 2003 Elsevier Science (USA). All rights reserved.