Modification of the second translation initiation site restricts the replication of foot-and-mouth disease virus in PK-15 cells

文献类型： 外文期刊

第一作者： Yuan, Hong

作者： Yuan, Hong;Li, Na;Li, Pinghua;Bai, Xingwen;Sun, Pu;Bao, Huifang;Gong, Xiaohua;Ma, Xueqing;Cao, Yimei;Li, Kun;Fu, Yuanfang;Zhang, Jing;Li, Dong;Chen, Yingli;Zhang, Jie;Lu, Zengjun;Liu, Zaixin

作者机构：

关键词： FMDV; Vaccine; Virus replication; Translation initiation; Leader protein

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：4.813； 五年影响因子：4.697 ）

ISSN： 0175-7598

年卷期： 2020 年 104 卷 19 期

页码：

收录情况： SCI

摘要： The translation initiation of foot-and-mouth disease virus (FMDV) occurs at two alternative initiation sites (Lab AUG and Lb AUG). Usually, the Lb AUG is more favorably used to initiate protein synthesis than the Lab AUG. To explore the effect of Lb AUG on FMDV replication and obtain FMDV with restricted replication, this initiation codon was mutated to a variety of non-AUG codons (UGG, AUC, CUG, and AAA). Fortunately, the modifications did not prevent viral viability but influenced replication characteristics of some FMDV mutants in a cell-specific manner, as was shown by the similar replication in BHK-21 cells and delayed growth kinetics in PK-15 cells. This attenuated phenotype of FMDV mutants in PK-15 cells was found to be correlated with reduced abilities to cleave eIF4GI and suppress interference (IFN) expression. As leader (L) protein was reported to be responsible for eIF4GI cleavage and inhibition of IFN expression, the in vivo L protein synthesis was examined during the infection of FMDV mutants. Our results showed that not only the total yield of L proteins was severely influenced but also the individual yield of L protein was seen to be affected, which implied that both the relative usage of the two initiation sites and overall translation efficiency were changed by Lb AUG modifications. In addition, the in vitro translation activity was also negatively regulated by Lb AUG mutations. Collectively, these findings suggested that the restricted replications of Lb AUG-modified FMDVs were related to the delayed eIF4GI cleavage and decreased ability to block IFN expression but were mainly determined by the inefficient translation initiation. FMDVs precisely with modifications of Lb AUG initiation codon may represent safer seed viruses for vaccine production.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序