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. 2005 Jan;79(2):812–822. doi: 10.1128/JVI.79.2.812-822.2005

TABLE 3.

Effect of resistance mutation in the RT on the inhibition of viral replication in P4 cells pretreated with hydroxyurea as measured by a single-cycle viral replication assaya

Mutant TAMs Other NRTIb mutation(s) NNRTI mutation(s) Polymorphisms Mean IC50 (μM) (SEM)
WT
    1 (pNL4-3) 102Q, 122K, 162C 669 (141)
    2 83K, 122K, 123E, 135T, 162A, 177E, 211K, 214F 777 (197)−
    3 39N, 64R, 123S, 135V, 162C, 173A, 174K, 177D/E, 200A, 207A, 211S, 214F 483 (153)−
    4 178L, 169E/D 364 (136)−
M184V present
    5 (M184V) 184V 102Q, 122K, 162C 84 (4)*
    6 184V 83K, 122E, 123D/E, 200T/A, 214F 211 (52)*
    7 184V 49R, 122E, 177E, 202V 146 (43)**
    8 41L, 215Y 184V 101Q 121C, 135T, 162C, 178L, 211K, 214F 49 (11)**
    20 67N, 215Y 101K/N/Q/H, 181C 72I, 74I, 75I, 86G, 89K, 91P, 93K, 95A, 136Q, 137H, 139M, 142V, 162Y, 177E, 207E, 214F 562 (129)−
    21 67N, 70R 98S 44K, 47N, 48T, 54K, 102K, 122Q, 123N, 166R, 177E, 211K, 214F 382 (103)−
3 TAMs
    22 67D, 70R, 219Q 98G 122K, 162N/D 120 (38)*
    23 41L, 210W, 215Y 43S, 121H, 135T, 143R/K, 177E, 211K, 214F 424 (112)−
    24 41L, 67N, 215Y 42E, 86E, 110D/N, 122K, 135V, 147N/K, 162C, 178L, 204A, 207E, 214F 826 (211)−
    25 41L, 67N, 215Y 122E, 135V, 200I, 211K, 214F 404 (88)−
    26 41L, 210W, 215Y 135T, 178L, 211K, 214F 195 (53)*
5 TAMs
    27 41M/L, 67N, 70R, 215F, 219Q 101E 122K, 123E, 135I/V, 162Y, 211K, 214F 147 (18)**
    28 41L, 67N, 70R, 103N, 181C 69E, 122K, 135T, 150L/Q/M, 162Y, 70 (3)**
    9 41L, 210W, 215Y 184V 39K, 43K, 122K, 214F 101 (22)**
    10 62V, 151M, 184V 68G, 83K, 122K, 135K, 143S/G, 162A, 203E/D, 207Q/E, 211K, 214L/F 89 (10)**
    11 41L, 67N, 210W, 215Y 184V 122K, 123E, 177E, 202V, 211K, 214F, 245E 103 (26)**
Other RT mutations present
    12 (BV34) 41L, 67N, 70R, 215F, 219Q 74I, 75L NAc 42 (4)**
    13 151M 181C 102Q, 122K, 162C 107 (13)**
    14 215Y, 219K/Q 69S + VA, 62A, 74V 98G, 181C, 190A 83K, 200A, 203D 46 (6)**
    15 41L, 70R, 219E 65R, 75I, 151M, 178M 103N, 108I, 190A 68G, 112S, 121D/M, 142V, 177E, 211A, 214F 61 (4)**
    16 41L, 67E, 210W, 215Y 69S + SV, 62V, 74V, 118V/I 98S, 101K/Q, 103N, 108V/I, 181C, 190A 39A, 135T, 178I/L, 189V/I, 196E, 203D, 211K, 214F, 228R 47 (4)**
2 TAMs
    17 (41 + 215) 41L, 215Y 102Q, 122K, 162C 251 (45)*
    18 41L, 215Y 103N, 181C 102Q, 122E, 135T, 142V, 162C, 200A, 228R 161 (36)*
    19 210L/W, 215Y, 215F, 219Q 49R, 83K, 178I/M, 196G/E, 211Q, 177G, 214F, 218E, 228H, 247R 123 (8)*
a

Viral infectivity in hydroxyurea-pretreated cells was evaluated as described in the Fig. 5 legend with RTs amplified from 25 clinical isolates and the recombinant virions used in the evaluation of DNA synthesis. IC50s were calculated by fitting the optical density data to a sigmoid curve. For each viral population studied, both the RT genotype and the IC50 for the inhibition of viral replication in hydroxyurea-pretreated cells were determined. The results are the means of four to six independent experiments. Statistical analysis was performed using analysis of variance (P < 0.0001), followed by the Newman-Keuls multiple-comparison test. −, not significantly different from the WT pNL4-3 virus; *, P < 0.01 compared to the WT pNL4-3 virus; **, P < 0.001 compared to the WT pNL4-3 virus.

b

NRTI, nucleoside RT inhibitor.

c

NA, not applicable.