Fig. 1.

Cellular Signaling Analysis of Drug Stimulated Cells. A. Host cells were treated with the five drug combinations listed in Table 1 as well as each individual drugs. As a reminder: high dose IFNs and ACV (Optimal_A and Optimal_AA), high dose RIB and ACV (Optimal_B), low dose IFNs and ACV (Subopt_A), and low dose IFNs and RIB (Subopt_B). Drug treatments are indicated at the bottom of the panel. Samples were collected 0.5, 4, 8, and 16 h after drug stimulations. Although 12 phosphoproteins were examined for each sample (pAkt, pERK, pJNK, p-cJun, pMAPKAPK2, pNFĸB, p-p38, pS6, pSTAT1, pSTAT3, pSTAT5, and pSTAT6), here we show only pS6 and pSTAT1. The complete panel is shown in Supplementary Fig. 1. B. Comparison of pSTAT1 and pS6 signaling after 16 h of individual drug treatments indicates IFN up-regulated pSTAT1 signaling and RIB down-regulated pS6 signaling. C. Comparison of two optimal drug combination treatments shows that the IFN-rich treatment up-regulated pSTAT1 signaling and RIB-rich treatment down-regulated pS6 signaling. All experimental data shown is representative data from three independent experiments. Flow cytometry histograms are color-coded as in a heatmap with black being unchanged and shades of yellow denoting increases. Quantitation of plots from B and C are shown in Supplemental Fig. 2.