title: 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.
abstract: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory 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 proteins 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 localization were assessed using Wes tern blotting and indirect immunofluorescence. While ORF 4b demonstrated majorly nuclear localization, all of the other proteins demonstrated cytoplasmic localization. In addition, for the first time, our experiments revealed that the M, ORF 4a, ORF 4b, and ORF 5 proteins are potent interferon antagonists. Further examination 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-β promoter activity, IRF-3/7 and NF-κB activation) and ISRE promoter element signaling pathways. Together, our results provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.
authors: Key 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.
authors: Yang
authors: Y
authors: Yang
authors: Ling
authors: L
authors: Zhang
authors: Heyuan
authors: H
authors: Geng
authors: Yao
authors: Y
authors: Deng
authors: Baoying
authors: B
authors: Huang
authors: Yin
authors: Y
authors: Guo
authors: Zhengdong
authors: Z
authors: Zhao
authors: Wenjie
authors: W
authors: Tan
mesh_terms: D002460:Cell Line; D017934:Coronavirus / Q000235:genetics* / Q000472:pathogenicity; D000086862:Coronavirus M Proteins; D005814:Genes, Viral; D006801:Humans; D007372:Interferons / Q000037:antagonists & inhibitors*; D016366:Open Reading Frames; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000086862:Coronavirus M Proteins; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins; D007372:Interferons