Table 2.
Mutations selected in viruses with wild-type proteases during the bevirimat in vitro selections
| Wild-type proteases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CA | p2 | ||||||||||||
| Gag position | 359 | 360 | 361 | 362 | 363 | 364 | 365 | 366 | 367 | 368 | 369 | 370 | 371 |
| HXB2 aa | K | A | R | V | L | A | E | A | M | S | Q | V | T |
|
WT HXB2 n = 10 |
- | - | - | - | - | V | - | - | - | - | - | - | - |
| - | - | - | - | - | - | - | - | - | - | - | A | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | V/I | - | - | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | V/I | - | A/V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
|
WT NL4-3 n = 10 |
- | - | - | - | - | A/V | - | A/V | - | - | - | - | - |
| - | - | - | - | - | A/V | - | - | - | - | - | V/A | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | A/V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
|
NC/p1 431V n = 4 |
- | - | - | - | - | V | - | - | - | - | - | - | - |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
|
NC/p1 436E-437T n = 4 |
- | - | - | - | - | V | - | - | - | - | - | - | - |
| - | - | - | V/I | - | A/V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
| - | - | - | - | - | V | - | - | - | - | - | - | - | |
Schematic representation of the amino acid changes appearing in the CA/p2 region during bevirimat in vitro selection experiments with wild-type HIV-1 or NC/p1 mutants. In vitro selections with wild-type viruses (HXB2 and NL4-3) were performed 10 times, the NC/p1 variants 5 times (n = 4 because one culture was discontinued for each virus). Mutations that previously have been identified in vitro as bevirimat resistance mutations are indicated in bold. The QVT-polymorphisms that are associated with a reduced response to bevirimat in vivo are underlined. The actual CA/p2 cleavage site is between amino acids 363 and 364.