Table 1.
Genotypic characterization of plaque-purified variants selected with GCV from a pretherapy clinical isolate
| Varianta | Genotype |
EC50, in μM (ratio)c |
|||
|---|---|---|---|---|---|
| UL97 | UL54b | GCV | CDV | FOS | |
| Clinical isolate | WT | Baseline | 1.9 | 0.53 | 21.8 |
| 10 GCV-1 A | WT | P488R | 14.3 (7.5) | 3.9 (7.4) | 21.3 (1.0) |
| 10 GCV-1 B | WT | C539R | 12.0 (6.3) | NAd | NA |
| 25 GCV-1 A | H520Q | C539R, F595I | 113 (59) | 3.8 (7.4) | NA |
| 25 GCV-1 B | G598D | C539R, F595I | 52.5 (28) | NA | NA |
| 50 GCV-1 A, Be | H520Q | C539R, F595I | 150 (79) | 6.9 (13) | 137 (6.3) |
| 300 GCV-1 A | H520Q | C539R, F595I | NA | NA | NA |
| 300 GCV-1 B | H520Q | C539R | NA | NA | NA |
| 1,000 GCV-1 A | H520Q | C539R, V787L, L862F, V946L | NA | NA | NA |
| 1,000 GCV-1 B | H520Q | C539R, V787L, V946L | NA | NA | NA |
a
Numbers indicate GCV concentration at which at least two different clones (A and B) were plaque purified.
b
Only variations from the baseline UL54 sequence are shown.
c
EC50 values were obtained using a standardized PRA (33). Values in parentheses are EC50 ratios, which express the EC50 for the plaque-purified variant/EC50 for the pretherapy clinical isolate.
d
NA, not available. The unpurified virus obtained at 1,000 μM had a GCV EC50 value of 512 μM.
e
The two different clones analyzed (A and B) had identical genotypes.