Schematic of the HIV-1 genome and the shRNA inhibitors. (A) The shRNA wt targets HIV-1 integrase (int). The wt target sequence is shown below together with the G8A and G15A escape mutations. (B) Depicted are the shRNAs against the integrase target. Indicated in red are the mutated nucleotides to construct the 2nd generation shRNAs that target the G8A and G15A escape viruses. (C) The primary shRNA-wt and the 2nd generation shRNA-G8A and shRNA-G15A cassettes were cloned in the lentiviral vector JS1 under control of the polymerase III promoters H1, 7SK and U6, respectively. All three shRNA cassettes were combined in the shRNA-combi vector.