TABLE 3.
Phenotypic susceptibility to BVM and genotypic data for the mutants with site-directed mutations
| Isolate no.a | BVM FCb | Amino acid change at the indicated position in the following protein: |
||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Capsidc |
SP1d |
|||||||||||||||||||||
| 357 (G)e | 358 (H) | 359 (K) | 360 (A) | 361 (R) | 362 (V) | 363 (L) | 364 (A) | 365 (E) | 366 (A) | 367 (M) | 368 (S) | 369 (Q) | 370 (V) | 371 (T) | 372 (N) | 373 (S) | 374 (A) | 375 (T) | 376 (I) | 377 (M) | ||
| 1 | >100** | —g | — | — | — | — | — | — | — | — | — | — | C | — | A | Delf | — | — | — | — | — | — |
| SDM-1 (wt SP1) | 0.6 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| 3 | >100** | S | — | — | — | — | — | — | — | — | — | — | — | — | A | Del | H/N | — | — | — | — | — |
| SDM-3 (wt SP1) | 0.7 | S | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| 6 | >100** | — | — | — | — | — | — | — | — | — | — | — | — | — | A | — | — | A | T | — | — | — |
| SDM-6a (wt SP1) | 0.4* | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| SDM-6b (wt V370) | 0.7 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | A | T | — | — | — |
| SDM-6c (wt S373/A374) | >100** | — | — | — | — | — | — | — | — | — | — | — | — | — | A | — | — | — | — | — | — | — |
| 7 | 1 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| SDM-7 (V362I) | >100** | — | — | — | — | — | I | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| 8 | 1.2 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| SDM-8 (V362I) | >100* | — | — | — | — | — | I | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| LAI | 1 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| SDM-LAI (V362I) | >100** | — | — | — | — | — | I | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| 12 | >100** | S | — | — | — | — | I | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
| SDM-12 (wt V362) | 0.7 | S | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — | — |
Mutants constructed by site-directed mutagenesis (SDM) were created by PCR from patient-derived isolates (isolates 1, 3, 6, 7, 8, and 12) or the LAI laboratory strain, with the specific changes in SP1 (isolates 1, 3, and 6) or the capsid protein (V362I; isolates 7, 8, 12 and LAI laboratory strain) being as shown. All other protease and Gag sequence were identical to those in the patient isolate or laboratory strain. wt, wild type.
Fold change (FC) in the bevirimat EC50 compared to wild-type EC50 of 34 nM against HIV-1 LAI. The statistical significance of the fold changes in EC50s compared to the wild-type EC50 is expressed as follows P < 0.01 (**) and P < 0.05 (*). The results are the averages of at least three independent experiments.
The last 7 amino acids of the Gag-capsid protein sequences are shown.
The complete amino acid sequences of the Gag-SP1 protein are shown (14 residues).
The letters in parentheses represent the wild-type sequence.
Del, deletion.
—, same as wild type.