April 2016 Vol.4 No.3

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Original Research Article

The role of the active site amino acids of the 2A protease in the translation of EV71 RNA

Ni Xuefei¹, Xu Chao², Xiong Qing², Peng Yihong², Wang Linghang¹ and Li Xingwang^1*

¹Infection Disease Center, Beijing DiTan Hospital affiliated to Capital Medical University, Beijing100015, People’s Republic of China
²Microbiology Department, Peking University Health Science Center, Beijing100191, People’s Republic of China

*Corresponding Author’s Email: ditanlxw@163.com
Tel.: 15611973658

Accepted April 13, 2016

Abstract

Hand, foot and mouth disease was an acute infectious disease. Severe cases were caused primarily by enterovirus 71. The 2A protease of enterovirus 71 was a cysteine protease with cis-and trans-cleavage activities. The 2A protease blocked Cap-mediated translation initiation, and active site mutants exhibited different levels of reduction of translation. The D39E and C110A mutants were as effective as the wild-type 2A protease in blocking cap-dependent translation, but the H21N mutant caused only a minor reduction in Cap-dependent translation initiation. Furthermore, double mutants and a triple mutant of 2A protease did not have a significant effect on cap-mediated translation initiation. However, an enterovirus 71 2A replicon promoted IRES-mediated translation initiation, but an enterovirus 71 2A mutant replicon did not. These data suggested that the enzymatic activity of the 2A protease inhibited host protein synthesis by cleaving eIFs and PABP and contributes to the translation of enterovirus 71 RNA. Thus, the 2A protease played an important role in the pathogenesis of enterovirus 71.

Keywords: 2A protease, Amino acids, Enterovirus 71RNA, Enzyme active sites, Translation