Day Craig W, Smee Donald F, Julander Justin G, Yamshchikov Vladimir F, Sidwell Robert W, Morrey John D
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 4700 Old Main Hill, Utah State University, Logan, UT 84322-4700, USA.
Antiviral Res. 2005 Jul;67(1):38-45. doi: 10.1016/j.antiviral.2005.04.002.
Ribavirin has been reported to cause error-prone replication and viral extinction in RNA viruses. The antiviral activity of ribavirin against West Nile virus (WNV) was evaluated in various cell lines to select a model in which mutagenic effects could be studied. The antiviral activity was greatest in HeLa cells as compared to CV-1, L929, Vero, or MA-104 cells. WNV was also passaged sequentially in cell monolayers treated with ribavirin to determine whether cumulative mutations could lead to viral extinction in these cell lines. The virus was abrogated in HeLa cells after 4 passages, while high viral titers persisted after many passages in other cells. A molecular clone of WNV was propagated in HeLa cells treated with 15 microg/mL ribavirin, and sequencing of viral genome segments revealed significant increases in transition mutations, demonstrating that ribavirin induced error-prone replication. The relative infectivity of viral RNA synthesized in the presence of ribavirin was shown to be reduced compared with untreated controls. These data support the hypothesis that error catastrophe is one of the modes of action for ribavirin against WNV.
据报道，利巴韦林可导致RNA病毒发生易出错复制并使病毒灭绝。在各种细胞系中评估了利巴韦林对西尼罗河病毒（WNV）的抗病毒活性，以选择一个可研究诱变作用的模型。与CV-1、L929、Vero或MA-104细胞相比，利巴韦林在HeLa细胞中的抗病毒活性最强。WNV也在经利巴韦林处理的细胞单层中连续传代，以确定累积突变是否会导致这些细胞系中的病毒灭绝。病毒在HeLa细胞中传代4次后被消除，而在其他细胞中多次传代后仍保持高病毒滴度。WNV的分子克隆在经15μg/mL利巴韦林处理的HeLa细胞中增殖，病毒基因组片段测序显示转换突变显著增加，表明利巴韦林诱导了易出错复制。与未处理的对照相比，在利巴韦林存在下合成的病毒RNA的相对感染性降低。这些数据支持了错误灾难是利巴韦林对抗WNV的作用模式之一这一假说。
