Ribavirin Can Be Mutagenic for Arenaviruses
Ribavirin Can Be Mutagenic for Arenaviruses
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DOI：
10.1128/jvi.00614-11
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发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Martin, Veronica
中科院分区：
文献类型：
--
作者：
Moreno, Hector;Gallego, Isabel;Martin, Veronica
沙粒病毒包括几种重要的人类病原体，对抗这些病毒的预防或治疗干预措施的选择非常有限。超说明书使用嘌呤核苷类似物利巴韦林（1-β-D-呋喃核糖基-1-H-1,2,4-三唑-3-甲酰胺）是目前唯一可用于沙粒病毒感染的抗病毒治疗。然而，利巴韦林针对沙粒病毒的抗病毒机制仍不清楚。在这里，我们证明利巴韦林对细胞培养物中的原型沙粒病毒淋巴细胞性脉络膜脑膜炎病毒（LCMV）具有诱变作用。在单次和多次传代方案下观察到利巴韦林对 LCMV 的诱变活性，并且不能用利巴韦林介导的肌苷单磷酸脱氢酶 (IMPDH) 抑制促进的细胞内 GTP 库减少来解释。我们的研究结果表明，利巴韦林对沙粒病毒的抗病毒活性可能至少部分是通过致死诱变发挥的。讨论了抗沙粒病毒治疗的意义。
Arenaviruses include several important human pathogens, and there are very limited options of preventive or therapeutic interventions to combat these viruses. An off-label use of the purine nucleoside analogue ribavirin (1-beta-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is the only antiviral treatment currently available for arenavirus infections. However, the ribavirin antiviral mechanism action against arenaviruses remains unknown. Here we document that ribavirin is mutagenic for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) in cell culture. The mutagenic activity of ribavirin on LCMV was observed under single-and multiple-passage regimes and could not be accounted for by a decrease of the intracellular GTP pool promoted by ribavirin-mediated inhibition of inosine monophosphate dehydrogenase (IMPDH). Our findings suggest that the antiviral activity of ribavirin on arenaviruses might be exerted, at least partially, by lethal mutagenesis. Implications for antiarenavirus therapy are discussed.