Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy
J. Clin. Invest. Ilona Hauber, et al. 115:76 doi:10.1172/JCI21949 [
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Figure 4Kinetics of HIV-1 inhibition by CNI-1493 and long-term drug exposure. (
A) PM1 cells were infected with HIV-1 BaL and cultured for 12 days in the presence of CNI-1493 at a concentration of 0.5 μM. Subsequently, the cells were split in 2 equal halves (Cell-split). One of these cultures was further incubated in culture medium containing 0.5 μM CNI-1493 for another 12 days. The other culture was washed with medium and incubated for 12 days in the presence of DMSO (solvent control). The culture medium was changed at days 2, 5, 7, 10, and 12 before the drug was removed, and at days 2, 5, 7, and 9 after cell splitting. The viability of the cells, cell counts, and p24 antigen levels were determined at the days indicated. (
B) HIV-1 BaL–infected PM1 cells were cultured for 12 weeks in the presence of 125 nM CNI-1493. Subsequently, the virus-containing supernatant was used for de novo infection of another batch of PM1 cells, and culturing of these cells, as well as of cells infected with wild-type (WT) HIV-1 BaL, continued for an additional 16 days in the presence of 1.0 μM CNI-1493 or DMSO (solvent control). Inhibition of virus replication (in percent; black bars) and drug toxicity (as measured by MTT assay; gray bars) at days 8, 12, and 16 are indicated.