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

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Previous studies have shown that the FMDV Asia1/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 3Dpol fidelity of type Asia1 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 3Dpol 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.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalVirology
Volume518
DOIs
StatePublished - May 2018

All Science Journal Classification (ASJC) codes

  • Virology

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