TABLE 3.
Resistance profiles of viral clones constructed by site-directed mutagenesisa
| Mutation(s) at codons | Mutant | NRTI resistance profileb
|
|||||
|---|---|---|---|---|---|---|---|
| Zidovudine
|
Lamivudine
|
Abacavir
|
|||||
| RF | n | RF | n | RF | n | ||
| 44 | MW01 | 2.0 (1.2) | 5 | 1.3 (0.4) | 16 | 1.3 (0.5) | 15 |
| 118 | MW02 | 1.0 (0) | 5 | 1.9 (1.0) | 7 | 1.2 (0.3) | 6 |
| 184 | MW03 | 1.4 (0.5) | 5 | >100 (NA) | 16 | 1.5 (0.6) | 15 |
| 44/118 | MW04 | 1.2 (0.3) | 5 | 6.2 (2.6) | 5 | 2.2 (0.6) | 5 |
| 44/184 | MW05 | 1.2 (0.3) | 5 | >100 (NA) | 15 | 3.1 (1.2) | 14 |
| 118/184 | MW06 | 1.0 (0) | 5 | >100 (NA) | 7 | 1.8 (0.6) | 6 |
| 44/118/184 | MW07 | 1.0 (0) | 5 | >100 (NA) | 7 | 3.1 (1.3) | 7 |
| 41/210/211/215 | MW08 | >100 (NA) | 6 | 3.0 (0.6) | 7 | 3.8 (0.8) | 8 |
| 41/44/118/210/211/215 | MW09 | >100 (NA) | 4 | 6.2 (1.8) | 5 | 4.7 (1.9) | 7 |
| 41/184/210/211/215 | MW10 | 51.0 (24.0) | 4 | >100 (NA) | 5 | 8.0 (3.7) | 7 |
| 41/44/118/184/210/211/215 | MW11 | 32.2 (20.6) | 5 | >100 (NA) | 6 | 7.9 (2.3) | 8 |
a
Mutations that were inserted into the pNL4-3 backbone were M41L, E44D, V118I, M184V, L210W, R211K, and T215Y. Recombinant viruses from viral clones with 211R and 214L (44/118/210/215, 44/118/184/215, 41/44/118/184/215, and 44/118/184/210/215) replicated so poorly that resistance testing could not be performed.
b
RF, fold increase in IC50 compared with the nonresistant reference virus NL4-3; n, number of independent runs for each phenotypic resistance testing; NA, not applicable, because endpoint of resistance was not determined. Standard errors are included in parentheses.