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. 2015 Sep 1;5:13344. doi: 10.1038/srep13344

Figure 2. Kinase activity of MKNK1 promotes IRES-dependent translation and HCV infection.

Figure 2

(a) A specific inhibitor of MKNK1 kinase activity preferentially impairs IRES-dependent over CAP-dependent luciferase reporter translation. Huh7.5 cells incubated for one hour with increasing doses of MKNK1 inhibitor. Treated cells were co-transfected with reporter mRNAs (IRES-firefly and cap-renilla) for four hours prior measuring of the firefly and renilla luciferase activity as described in the methods section. Data are expressed as means of the ratio of firefly/renilla luciferase activity +/− SEM. *p < 0.01 (Student’s t-test, n = 15 of three independent experiments). (b) MKNK1 inhibitor has only a minor impact on cell viability of Huh7.5 cells. After 5 h incubation with increasing concentrations of MKNK1 inhibitor the cell number was assessed by counting and the cell viability was assessed using Presto Blue. Data are expressed as means +/− SEM (n = 3 of one representative experiment). (c) MKNK1 inhibitor significantly and dose-dependently inhibits HCV infection at absent cell toxicity. Huh7.5.1 cells were pre-treated for one hour with increasing concentrations of MKNK1 inhibitor prior infection with cell culture-derived HCV (strain Luc-Jc1). Infected cells were maintained in the presence of the respective MKNK1 inhibitor concentration prior cell lysis and the measurement of the luciferase activity at day three. Data are expressed as means +/− SEM. *p < 0.01 (Student’s t-test, n = 3 of one representative experiment). All inhibitor dilutions and controls in this figure were prepared in a constant background of 1% DMSO.