RESUMO
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.
Assuntos
Humanos , Linhagem Celular , Coronavirus , Genética , Virulência , Genes Virais , Interferons , Fases de Leitura Aberta , Proteínas Recombinantes , Genética , Metabolismo , Proteínas da Matriz Viral , Genética , Metabolismo , Proteínas Virais Reguladoras e Acessórias , Genética , Metabolismo , Proteínas Estruturais Virais , Genética , MetabolismoRESUMO
Iretreatment with tea polyphenol (TP) at a dose of 10mg/kg ip to rats five days before isoproterenol (ISO) challenge (1mg/kg sc, for two days), resulted in decreases of malonydialdehyde concentration, creatine phosphokinase, lactic dehydrogenase (LDH) and LDH1,activities; increased LDH2/LDH1 ratio and inhibited the extent of myocardial injury, similar to the action of propranol. At the same time TP decreased rat plasma renin activity.The results suggested that the mechanism by which TP protects heart from ISO-induced myocardial injury is due to its antioxygen free radical and inhibition of renin activities.