Table 1.
shRNA name |
HIV-1 target |
HIV-1 inhibition |
Target conservation (%)5 |
Viral escape6 |
Lentiviral vector |
Cell toxicity9 |
Drug resistance mutation10 | |||||
Position1 | Gene | Transient3 | Stable4 | Subtype B | All subtypes | Vector targeting7 | Titer reduction8 | In vitro | In vivo | |||
LDR2 | 327 | Leader | 95 | ++ | 66 | 61 | ND | + | ND | ND | ND | - |
LDR3 | 3282 | Leader | 94 | ++ | 68 | 61 | ND | + | ND | ND | ND | - |
LDR4 | 3292 | Leader | 99 | +++ | 68 | 61 | ND | + | ND | ND | ND | - |
LDR5 | 3302 | Leader | 94 | ++ | 68 | 61 | ND | + | ND | ND | ND | - |
LDR7 | 3322 | Leader | 84 | - | 69 | 61 | ND | + | ND | ND | ND | - |
LDR8 | 3332 | Leader | 79 | ++ | 69 | 61 | ND | + | ND | ND | ND | - |
LDR9 | 3342 | Leader | 91 | +++ | 70 | 63 | ND | + | ND | ND | ND | - |
CA | 1032 | CA-p24 | 97 | - | 87 | 67 | ND | - | - | - | ND | - |
Gag5 | 1365 | CA-p24 | 86 | ++ | 81 | 80 | + | - | + | + | + | - |
Pol111 | 19102 | Prot11 | 9711 | +++11 | 8911 | 8511 | +11 | -11 | -11 | -11 | -11 | D30N, V32I11 |
Pol2 | 19112 | Prot | 86 | - | 89 | 85 | ND | - | ND | ND | ND | D30N, V32I |
Pro 1 | 19122 | Prot | 99 | +++ | 85 | 81 | ND | - | - | - | ND | D30N, V32I |
Pro 2 | 19132 | Prot | 99 | ND | 80 | 79 | ND | - | ND | ND | ND | D30N, V32I |
Pro 3 | 19142 | Prot | 99 | ND | 80 | 79 | ND | - | ND | ND | ND | D30N, V32I |
Pro 4 | 19152 | Prot | 98 | ND | 77 | 76 | ND | - | ND | ND | ND | D30N, V32I, L33F |
Pro 5 | 19162 | Prot | 97 | ND | 79 | 78 | ND | - | ND | ND | ND | D30N, V32I, L33F |
Pro 6 | 19182 | Prot | 98 | ND | 78 | 77 | ND | - | ND | ND | ND | D30N, V32I, L33F |
Pro 7 | 19192 | Prot | 98 | ND | 77 | 76 | ND | - | ND | ND | ND | D30N, V32I, L33F |
Pro 8 | 2026 | RT | 87 | ND | 58 | 17 | ND | - | ND | ND | ND | D30N, V32I, L33F |
Pol6 | 37552 | RT | 97 | - | 72 | 75 | ND | - | ND | ND | ND | - |
RT 1 (A) | 37572 | RT | 95 | ++ | 71 | 74 | ND | - | - | - | ND | - |
RT 2 (B) | 37582 | RT | 98 | ++ | 73 | 75 | ND | - | - | + | ND | - |
RT 3 (C) | 37592 | RT | 95 | ++ | 73 | 75 | ND | - | - | - | ND | - |
RT 4 (F) | 37602 | RT | 85 | ++ | 69 | 69 | ND | - | ND | ND | ND | - |
RT 5 (G) | 37622 | RT | 94 | - | 72 | 72 | ND | - | - | - | ND | - |
Int 1 | 4310 | Int | 91 | ND | 71 | 19 | ND | - | ND | ND | ND | - |
Int 2 | 4344 | Int | 96 | +++ | 67 | 25 | ND | + | + | - | ND | - |
Pol29 | 4393 | Int | 82 | - | 80 | 80 | ND | + | ND | ND | ND | - |
Int 3 | 44202 | Int | 95 | +++ | 68 | 61 | ND | + | + | + | ND | - |
Int 4 | 44222 | Int | 99 | ND | 71 | 64 | ND | + | ND | ND | ND | - |
Int 5 | 4491 | Int | 81 | ND | 70 | 33 | ND | - | ND | ND | ND | - |
Pol45 | 45432 | Int | 92 | ++ | 91 | 75 | ND | - | ND | ND | ND | - |
Pol4711 | 45452 | Int11 | 9211 | +++11 | 9111 | 7311 | +11 | -11 | -11 | -11 | -11 | -11 |
Vif | 4646 | Int/Vif | 96 | - | 82 | 31 | ND | - | - | - | ND | - |
R/T511 | 5551 | Rev/Tat11 | 9311 | +++11 | 8711 | 7311 | +11 | -11 | -11 | -11 | -11 | -11 |
Env 1 | 7250 | gp120 | 81 | ND | 83 | 76 | ND | + | ND | ND | ND | - |
Env 2 | 78752 | gp41 | 83 | ND | 49 | 33 | ND | - | ND | ND | ND | - |
Env 3 | 78812 | gp41 | 89 | ND | 19 | 6 | ND | + | ND | ND | ND | - |
Env 4 | 78842 | gp41 | 85 | ND | 21 | 6 | ND | + | ND | ND | ND | - |
Env 5 | 8026 | gp41 | 96 | +++ | 53 | 14 | ND | + | + | + | ND | - |
Env 6 | 82772 | gp41 | 98 | ++ | 53 | 18 | ND | - | - | + | ND | - |
Env 7 | 82782 | gp41 | 98 | ++ | 56 | 18 | ND | - | - | - | ND | - |
Env 8 | 8359 | gp41 | 97 | +++ | 3 | 1 | ND | - | - | - | ND | - |
LTR | 9072 | 3’LTR | 95 | ++ | 53 | 1 | ND | - | - | - | ND | - |
Position in human immunodeficiency virus type 1 (HIV-1) LAI mRNA;
Overlapping short hairpin RNA (shRNA) clusters;
Percentage of inhibition of HIV-1 production in co-transfected cells;
Inhibition of HIV-1 replication in stably transduced cells: +++ = strong, ++ = medium, + = low, - = no inhibition;
Percentage of sequences in Los Alamos database identical to shRNA target sequence;
Detection of escape mutations after prolonged culturing;
100% complementarity of the shRNA to JS1 lentiviral vector;
Titers compared to JS1 lentiviral vector; + = reduction > 1 log, - = reduction < 1 log;
Effects on cell growth; + = negative effect, - = no effect;
Drug resistance mutations in the shRNA target region;
Selected for the combinatorial gene therapy. ND: Not determined.