Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation

文献类型： 外文期刊

第一作者： Li, Chen

作者： Li, Chen;Wang, Haiwei;Yuan, Tiangang;Yang, Decheng;Zhou, Guohui;Yu, Li;Woodman, Andrew;Cameron, Craig E.

作者机构：

关键词： Foot-and-mouth disease virus; Polymerase; Fidelity; Fitness; Nucleoside analogue; Virulence

期刊名称：VIROLOGY （ 影响因子：3.616； 五年影响因子：3.967 ）

ISSN： 0042-6822

年卷期： 2018 年 518 卷

页码：

收录情况： SCI

摘要： Previous studies have shown that the FMDV Asial/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D(pol) fidelity of type Asial FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3D(pol) in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type o FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV.

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