TABLE 2.
Drug susceptibilities of recombinant HCMVs expressing single and double mutations in the UL54 gene
| UL54 genotype | IC50 (μM)a
|
|||
|---|---|---|---|---|
| GCV | CDV | PFA | ADV | |
| Wild type | 3.5 | 0.75 | 45 | 42 |
| F412C | 15 (4.3) | 13 (17) | 54 (1.2) | 10 (−4.2) |
| L802M | 3.9 (1.1) | 0.7 (0.9) | 140 (3.1) | 120 (2.8) |
| F412C L802M | 22 (6.2) | 12 (16) | 140 (3.1) | 25 (−1.7) |
| K513E | 17.5 (5.0) | 6.9 (9.2) | 50 (1.1) | 20 (−1.9) |
| D588E | 4.2 (1.2) | 0.8 (1.1) | 110 (2.4) | 84 (2.0) |
| K513E D558E | 23 (6.6) | 8.3 (11.1) | 120 (2.7) | 33 (−1.3) |
| K805Q | 3.5 (1.0) | 1.7 (2.2) | 8.0 (−5.6) | 8.9 (−4.8) |
| T821I | 15.8 (4.5) | 1.4 (1.9) | 950 (21) | 260 (6.4) |
| K805Q T821I | 15.1 (4.3) | 1.6 (2.1) | 455 (10.1) | 170 (4.0) |
a
The IC50 values represent averages from at least three determinations with two independently generated recombinant viruses. In all cases, the standard error was less than 35%. The boldface numbers indicate a significant (i.e., at least twofold) change in HCMV drug susceptibility. Positive and negative numbers in parentheses represent fold increases and decreases, respectively, in the IC50 values of the mutant virus relative to that for the UL54 wild-type recombinant virus.