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T135I substitution in the nonstructural protein 2C enhances foot-and-mouth disease virus replication

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Abstract

The foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays an important role in viral replication, virulence, and host range. It has been shown that deletions of 10 or 19–20 amino acids in the C-terminal half of 3A attenuate serotype O and C FMDVs, which replicate poorly in bovine cells but normally in porcine-derived cells, and the C-terminal half of 3A is not essential for serotype Asia1 FMDV replication in BHK-21 cells. In this study, we constructed a 3A deletion FMDV mutant based on a serotype O FMDV, the wild-type virus O/YS/CHA/05, with a 60-amino acid deletion in the 3A protein sequence, between residues 84 and 143. The rescued virus O/YS/CHA/05-Δ3A exhibited slower growth kinetics and formed smaller plaques compared to O/YS/CHA/05 in both BHK-21 and IBRS-2 cells, indicating that the 60-amino acid deletion in the 3A protein impaired FMDV replication. After 14 passages in BHK-21 cells, the replication capacity of the passaged virus O/YS/CHA/05-Δ3A-P14 returned to a level similar to the wild-type virus, suggesting that amino acid substitutions responsible for the enhanced replication capacity occurred in the genome of O/YS/CHA/05-Δ3A-P14. By sequence analysis, two amino acid substitutions, P153L in VP1 and T135I in 2C, were found in the O/YS/CHA/05-Δ3A-P14 genome compared to the O/YS/CHA/05-Δ3A genome. Subsequently, the amino acid substitutions VP1 P153L and 2C T135I were separately introduced into O/YS/CHA/05-Δ3A to rescue mutant viruses for examining their growth kinetics. Results showed that the 2C T135I instead of the VP1 P153L enhanced the virus replication capacity. The 2C T135I substitution also improved the replication of the wild-type virus, indicating that the effect of 2C T135I substitution on FMDV replication is not associated with the 3A deletion. Furthermore, our results showed that the T135I substitution in the nonstructural protein 2C enhanced O/YS/CHA/05 replication through promoting viral RNA synthesis.

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Acknowledgements

This work was supported by Grants from the State Key Laboratory of Veterinary Biotechnology (SKLVBP2015011) and a National Non-profit Institute Research Grant of CAAS-HVRI (No. 0302014017).

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Authors and Affiliations

  1. Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 678 Haping Road, Xiangfang District, Harbin, 150069, People’s Republic of China

    Tiangang Yuan, Haiwei Wang, Chen Li, Decheng Yang, Guohui Zhou & Li Yu

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  1. Tiangang Yuan
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  2. Haiwei Wang
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  3. Chen Li
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  4. Decheng Yang
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  5. Guohui Zhou
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  6. Li Yu
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Contributions

Li Yu and Haiwei Wang conceived and designed the study. Tiangang Yuan and Haiwei Wang carried out the experiments and wrote the manuscript. All authors read, revised, and approved the final manuscript.

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Correspondence to Haiwei Wang or Li Yu.

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Edited by Keizo Tomonaga.

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Yuan, T., Wang, H., Li, C. et al. T135I substitution in the nonstructural protein 2C enhances foot-and-mouth disease virus replication. Virus Genes 53, 840–847 (2017). https://doi.org/10.1007/s11262-017-1480-9

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  • DOI: https://doi.org/10.1007/s11262-017-1480-9

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