Table 4.
UL54 Varianta | Cidofovir |
Ganciclovir |
Foscarnet |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
EC50b | SDc | Nd | Ratioe | EC50b | SDc | Nd | Ratioe | EC50b | SDc | Nd | Ratioe | |
Control strains | ||||||||||||
wt | 0.21 | 0.06 | 134 | 1.06 | 0.3 | 124 | 39 | 10 | 132 | |||
I726V | 0.40 | 0.08 | 12 | 1.9 | 2.06 | 0.41 | 11 | 1.9 | 45 | 6 | 8 | 1.2 |
A809V | 140 | 32 | 87 | 3.6 | ||||||||
A987G | 0.94 | 0.29 | 120 | 4.5 | 5.37 | 1.33 | 9 | 5.1 | ||||
Newly phenotyped variants (N = 28) | ||||||||||||
Q229K | 0.20 | 0.06 | 8 | 1.0 | 1.32 | 0.19 | 11 | 1.2 | 47 | 15 | 10 | 1.2 |
D247N | 0.19 | 0.06 | 8 | 0.9 | 1.00 | 0.17 | 7 | 0.9 | 52 | 12 | 13 | 1.3 |
D262N | 0.22 | 0.03 | 8 | 1.0 | 1.16 | 0.17 | 7 | 1.1 | 45 | 16 | 10 | 1.2 |
T271A | 0.15 | 0.04 | 10 | 0.7 | 1.04 | 0.18 | 9 | 1.0 | 37 | 14 | 12 | 0.9 |
V284E | 0.22 | 0.06 | 8 | 1.1 | 1.28 | 0.14 | 8 | 1.2 | 47 | 16 | 18 | 1.2 |
D288N | 0.24 | 0.07 | 8 | 1.2 | 1.27 | 0.40 | 9 | 1.2 | 45 | 8 | 8 | 1.2 |
F396L | 0.20 | 0.06 | 8 | 0.9 | 1.51 | 0.30 | 10 | 1.4 | 35 | 7 | 14 | 0.9 |
L424V | 0.27 | 0.08 | 10 | 1.3 | 1.38 | 0.26 | 9 | 1.3 | 46 | 10 | 14 | 1.2 |
T437M | 0.21 | 0.07 | 8 | 1.0 | 1.05 | 0.18 | 8 | 1.0 | 31 | 9 | 8 | 0.8 |
F460L | 0.25 | 0.05 | 8 | 1.2 | 1.28 | 0.26 | 8 | 1.2 | 47 | 9 | 10 | 1.2 |
A505V | 0.39 | 0.14 | 26 | 1.9 | 1.97 | 0.60 | 27 | 1.9 | 41 | 13 | 9 | 1.0 |
A543S | 0.21 | 0.04 | 8 | 1.0 | 1.07 | 0.33 | 9 | 1.0 | 38 | 8 | 8 | 1.0 |
S612N | 0.21 | 0.04 | 14 | 1.0 | 0.97 | 0.26 | 10 | 0.9 | 29 | 7 | 7 | 0.7 |
V654G | 0.24 | 0.05 | 9 | 1.1 | 1.18 | 0.32 | 8 | 1.1 | 42 | 12 | 8 | 1.1 |
S660G | 0.18 | 0.01 | 10 | 0.9 | 1.05 | 0.32 | 11 | 1.0 | 43 | 9 | 8 | 1.1 |
S660N | 0.21 | 0.04 | 7 | 1.0 | 1.26 | 0.26 | 9 | 1.2 | 32 | 6 | 8 | 0.8 |
G667N | 0.17 | 0.05 | 8 | 0.8 | 0.91 | 0.31 | 12 | 0.9 | 39 | 5 | 10 | 1.0 |
A692G | 0.19 | 0.05 | 8 | 0.9 | 0.86 | 0.25 | 8 | 0.8 | 39 | 12 | 10 | 1.0 |
I726T | 0.36 | 0.09 | 10 | 1.7 | 2.14 | 0.59 | 11 | 2.0 | 42 | 9 | 8 | 1.1 |
E793V | 0.14 | 0.05 | 9 | 0.7 | 0.92 | 0.26 | 13 | 0.9 | 45 | 11 | 10 | 1.1 |
Q795P | 0.19 | 0.05 | 13 | 0.9 | 0.91 | 0.27 | 9 | 0.9 | 41 | 10 | 9 | 1.1 |
Q795R | 0.19 | 0.05 | 8 | 0.9 | 1.11 | 0.28 | 8 | 1.0 | 40 | 15 | 10 | 1.0 |
G841S | 0.22 | 0.09 | 12 | 1.1 | 2.30 | 0.64 | 15 | 2.2 | 83 | 18 | 7 | 2.1 |
P859A | 0.20 | 0.06 | 11 | 1.0 | 0.89 | 0.14 | 9 | 0.8 | 31 | 10 | 8 | 0.8 |
V902G | 0.21 | 0.07 | 10 | 1.0 | 1.27 | 0.36 | 9 | 1.2 | 39 | 9 | 10 | 1.0 |
E903G | 0.21 | 0.04 | 13 | 1.0 | 1.21 | 0.25 | 8 | 1.1 | 36 | 9 | 8 | 0.9 |
K947E | 0.22 | 0.07 | 7 | 1.0 | 1.03 | 0.34 | 13 | 1.0 | 41 | 7 | 8 | 1.1 |
M959T | 0.20 | 0.04 | 7 | 0.9 | 1.27 | 0.38 | 9 | 1.2 | 47 | 11 | 10 | 1.2 |
Bold: Results associated with decreased drug susceptibility.
Abbreviations: BAC, bacterial artificial chromosome; EC50, concentration required to reduce activity of the secreted alkaline phosphatase reporter by 50%; wt, wild type.
a Mutation introduced into BAC and recombinant virus.
b Mean drug concentration (µM) required to reduce secreted alkaline phosphatase growth by 50% at 6–7 days post infection.
c Standard deviation of the EC50 values.
d Number of assays (performed over at least 4 separate dates).
e Ratio of EC50 to baseline strain.