Figure 6

ADAM15 and γ-secretase are required for HIV-1 replication. (A) ADAM15 downregulation significantly reduced HIV-1 replication in U373-MAGI-CCR5. However, ADAM9 downregulation did not affect HIV-1 replication. U373 cells were transfected with siRNA and β-galactosidase was measured 48 h after infection with HIV-SF162. (B) Down-regulation of γ-secretase subunits significantly decreased HIV-1 replication. Presenilin-2, not presenilin-1, is specifically required for HIV-1 replication (P1 = presenilin-1, P2 = presenilin-2, PSEN = presenilin enhancer protein 2, **P < 0.01). β-galactosidase was measured 48 h after infection with HIV-SF162. (C) Serial dilutions of γ-secretase inhibitors (L-685,458 and DAPT) were added to the cells, and cell viability was assessed 24 h after addition of inhibitors. (D) L-685,458 and DAPT significantly reduced β-galactosidase in U373-MAGI-CCR5 cells compared to DMSO controls. β-galactosidase activity was measured 48 h after infection with HIV-SF162 (**P < 0.01).