TABLE 1.
Clone or wild type | Mutation |
n-Fold increase in IC50b
|
Neurovirulenced log (PFU/LD50) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
BVDU | BVaraU | ACV | GCV | PCV | PFA | PMEA | PMEDAP | HPMPC | HPMPA | |||
CI-1 | Ala 168 to Thr | ≥2,420 | >3,450 | 0.9 | 1.0 | 0.92 | 1.3 | 1.5 | 1.7 | 0.7 | 1.3 | 0.05 |
CI-5 | Ala 168 to Thr | ≥2,260 | ≥3,450 | 1.0 | 0.9 | 0.73 | 1.2 | 1.0 | 1.1 | 0.8 | 0.9 | 0.03 |
CI-24 | Arg 51 to Trp | 565 | >3,450 | 1,000 | 3,400 | 500 | 0.9 | 1.1 | 1.2 | 1.2 | 1.0 | 2.92 |
CI-28 | Arg 51 to Trp | 500 | >3,450 | 984 | 10,670 | 450 | 1.1 | 1.5 | 1.8 | 1.4 | 1.6 | 2.92 |
CI-3 | Gly 59 to Trp | ≥2,550 | >3,450 | 605 | 1,400 | 73 | 0.6 | 0.7 | 0.6 | 2.0 | 0.9 | 2.54 |
CI-27 | Gly 206 to Arg | ≥3,230 | >3,450 | ≥979 | 20,670 | >769 | 1.2 | 1.5 | 2.2 | 1.1 | 1.6 | 3.30 |
CI-2 | Arg 220 to His | >3,230 | >3,450 | 147 | 57 | 5.4 | 0.7 | 1.2 | 1.0 | 0.7 | 1.1 | 0.94 |
CI-22 | Tyr 239 to Ser | 113 | 931 | 247 | 180 | 20 | 1.0 | 1.5 | 1.5 | 0.8 | 1.1 | NDe |
CI-23 | Tyr 239 to Ser | 23 | 1,400 | 126 | 63 | 24 | 1.1 | 1.2 | 1.4 | 1.0 | 1.9 | 1.40 |
CI-29 | Gln 261 to stop | ≥3,230 | >3,450 | 468 | 667 | ≥769 | 1.5 | 1.5 | 2.5 | 1.8 | 2.5 | 3.68 |
CI-25 | Arg 281 to stop | ≥1,770 | >3,450 | 316 | 333 | ≥438 | 1.1 | 1.2 | 1.3 | 0.9 | 1.0 | 4.22 |
CI-34 | Thr 287 to Met | >3,230 | >3,450 | ≥1,050 | ≥33,330 | >769 | 1.0 | 0.8 | 1.5 | 1.3 | 2.3 | 2.07 |
CI-4 | 146 frameshift | ≥2,020 | >3,450 | 789 | 4,600 | >769 | 0.5 | 1.1 | 0.9 | 1.1 | 1.7 | 3.43 |
CI-15 | 185 frameshift | ≥3,230 | >3,450 | ≥947 | 6,270 | ≥627 | 1.1 | 1.5 | 1.0 | 1.3 | 0.7 | 2.5 |
CI-30 | 185 frameshift | >3,230 | ND | >1,050 | 14,000 | ≥769 | 1.3 | 1.5 | 1.6 | 0.9 | 1.1 | ND |
Wild type | 0.0062c | 0.0058 | 0.019 | 0.00015 | 0.026 | 19.6 | 7.4 | 1.91 | 0.114 | 0.035 | 0.05 |
Drug susceptibility profiles of BVDUr HSV-1 clones were determined in HEL cells.
The increase in IC50s was calculated from at least two independent experiments.
Mean IC50s were from seven independent experiments.
Neurovirulence of the different mutants was evaluated by intracerebral inoculation of the viruses into mice. The log (PFU/LD50) was determined as a reciprocal parameter of neurovirulence.
ND, not determined.