FIG 7.

Protein-protein interaction networks reveal synergistic drug effects. The PIN depicted in Fig. 6 revealed the convergence of PIM-1 activity and CDK2 activity. In two dose-matrix experiments, we thus tested whether the PIN prediction would translate into the ability of PIM-1 inhibitor IV–roscovitine (A) and AS601245–roscovitine (B) combinations to act in concert as inhibitors of PMA-induced HIV-1 reactivation. For this purpose, roscovitine was titrated over a concentration range from 0.01 to 10 μM, whereas the two reported PIM-1 inhibitors were cross-titrated over a concentration range from 0.01 to 10 μM. PMA-induced reactivation was then measured as the percentage of GFP-positive cells 48 h poststimulation. Cell viability was not affected by the treatment.