TABLE 2.
Mutations that arose upon selection in PAV-206a
| SC appearanceb | PAV-206 selection results |
Notes | |||
|---|---|---|---|---|---|
| Mutation no. relative to HXB2c | Mutation no. relative to NL4-3c | Frequency (%) of aad | Mutation associated with: | ||
| Nonsynonymous | |||||
| Dominant | V218M Gag (V86M p24 Gag) | V218M Gag (V86M p24 Gag) | V, 87.62 (8365); A, 4.85 (463); P, 3.40 (325) | Culture adaptation to intracellular CypA level (49, 50) | In the cyclophilin A binding loop |
| Dominant | N302Y Env (N272Y gp120) | N300Y Env (N270Y gp120) | N, 96.50 (6844); K, 1.06 (75) | Culture adaptation – CCR5 (104–106); fusion inhibitor resistance (52) | In the Env V3 loop; involved in coreceptor binding |
| Dominant | D547G Env (D36G gp41) | D545G Env (D36G gp41) | G, 99.65 (7069) | Replication advantage (53, 104); fusion inhibitor resistance (107) | In the Rev response element; in the T-20 (Enfuvirtide) drug binding site; D36 in NL4-3 but G36 in most other strains of HIV-1 (19) |
| ≥50% | Q550H Env (Q39H gp41) | Q548H Env (Q39H gp41) | Q, 99.17 (7035) | Culture adaptation (54); also arose in nelfinavir selection in the present study | In the rev response element; in the T-20 (enfuvirtide) drug binding site |
| Synonymous | |||||
| ≥50% | IATT 205 IATC Pol (IATT 50 IATC reverse trans.) | IATT 205 IATC Pol (IATT 50 IATC reverse trans.) | Unknown | ||
| ≥50% | QCAG 552 QCAA Env (QCAG 41 QCAA gp41) | QCAG 550 QCAA Env (QCAG 41 QCAA gp41) | Replication advantage (108) | In the Rev response element; in the T-20 (Enfuvirtide) drug binding site | |
| Dominant | VGTG 583 VGTA Env (VGTG 72 VGTA gp41) | VGTG 581 VGTA Env (VGTG 72 VGTA gp41) | Fusion inhibitor resistance (109) | In the Rev response element | |
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. Numbering of mutation 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).”