The structural and accessory proteins M,ORF 4a,ORF 4b,and ORF 5 of Middle East respiratory syndrome coronavirus(MERS-CoV)are potent interferon antagonists  

作　　者：Yang Yang Ling Zhang Heyuan Geng Yao Deng Baoying Huang Yin Guo Zhengdong Zhao Wenjie Tan 

机构地区：[1]Ke y Laboratory of Medical Virology,Ministry of Health,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China [2]Institute of Materia Medica(IMM),Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [3]Key Laboratory of Pathogen System Biology,Ministry of Health,Institute of Pathogen Biology,Chinese Academy of Medical Sciences,Beijing 100176,China

出　　处：《Protein & Cell》2013年第12期951-961,共11页蛋白质与细胞（英文版）

基　　金：This work was supported by the National Basic Research Program(973 Program)(No.2011CB504704);the Ministry of Health of China(2014ZX10004-001,2013ZX10004601).

摘　　要：The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of MERS-CoV and to determine whether any of these pro-teins acts as an interferon antagonist.Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl uorescence.While ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic localization.In addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon antagonists.Further exami-nation revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling pathways.Together,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.

关 键 词：MERS-CoV structural proteins accessory proteins interferon antagonists 

分 类 号：R37[医药卫生—病原生物学]