TABLE 1.
Nonsynonymous mutations that arose upon selection in nelfinavira
| SC appearanceb | Nelfinavir selection results |
Notes | |||
|---|---|---|---|---|---|
| Mutation no. relative to HXB2c | Mutation no. relative to NL4-3c | Frequency (%) of aad | Mutation associated with: | ||
| Dominant | H219Q Gag (H87Q p24 Gag) | H219Q Gag (H87Q p24 Gag) | H, 73.31 (6999); Q, 22.86 (2182); P, 1.73 (165) | Culture adaptation to intracellular CypA level (47, 49, 97); cyclosporine resistance (98) | In the cyclophilin A binding loop |
| ≥50% | A224T Gag (A92T p24 Gag) | A224T Gag (A92T p24 Gag) | A, 67.49 (6443); P, 31.35 (2993) | Culture adaptation (99) | In the cyclophilin A binding loop |
| ≥50% | L10F protease (L66F Pol) | L10F protease (L66F Pol) | L, 85.68 (4451); I, 7.10 (369); V, 5.47 (284) | Nelfinavir resistance (100); other PI resistance (45) | |
| Dominant | V77I protease (V133I Pol) | V77I protease (V133I Pol) | V, 83.10 (4322); I, 16.11 (838) | Nelfinavir resistance (42, 101) | |
| Dominant | L90M protease (L146M Pol) | L90M protease (L146M Pol) | L, 98.77 (5137); M, 1.15 (60) | Nelfinavir resistance (98); other PI resistance (45) | |
| ≥50% | S144R Env (S114R gp120) | S144R Env (S114R gp120) | S, 24.14 (1248); N, 21.88 (1131); T, 16.12 (833) | Fusion inhibitor resistance (102) | In the Env V1 loop |
| Dominant | A541V Env (A30V gp41) | A539V Env (A30V gp41) | A, 94.84 (6728); V, 2.93 (208); T, 1.97 (140) | Culture adaptation (51, 54); Rev inhibitor resistance (103) | In the Rev response element |
| Dominant | Q550H Env (Q39H gp41) | Q548H Env (Q39H gp41) | Q, 99.17 (7035) | Culture adaptation (54); also arose in PAV-206 selection in present study | In the Rev response element; in the T-20 (Enfuvirtide) drug binding site |
Mutations are numbered relative to the HXB2 or NL4-3 genomes, with the frequency of the mutation, the phenotype associated with the mutation, and relevant references indicated.
Gel sequencing chromatograms (SC) were visually inspected to identify a second chromatogram peak that is equal or larger in height than the peak corresponding to the reference sequence (defined here as ≥50%) or a single chromatogram peak that differs from the reference sequence (defined here as Dominant).
Indicates viral protein to which numbering refers, either in the HXB2 or NL4-3 HIV strain. The mutation number relative to other relevant proteins or domains is indicated in parentheses. Mutations in boldface are shown in Fig. 8.
Determined using AnalyzeAlign (available on Los Alamos HIV databases and compendiums site) using the premade Web Alignment; the top three that are >1% are listed. aa, amino acids. Entries are presented as follows: “amino acid, % frequency (number of isolates).”