TABLE 4.
LMV sensitivities and relative replication yields of wild-type HBV and its mutant derivativesa
| HBV variant | LMV EC50 (μM)b | Relative replication yieldc
|
Effect of L80I on replication efficiencyd
|
||
|---|---|---|---|---|---|
| Without LMV | With 1 μM LMV | Without LMV | With 1 μM LMV | ||
| Wild type | 0.41 ± 0.19 | 1.00 ± 0.15 | 0.33 ± 0.04 | ||
| rtL80I | 0.03 ± 0.01 | 0.57 ± 0.05 | 0.06 ± 0.01 | 43% decrease** | 82% decrease** |
| rtM204I | R | 0.18 ± 0.00 | 0.38 ± 0.04 | ||
| rtL80I/M204I | R | 0.39 ± 0.06 | 3.76 ± 0.43 | 117% increase* | 902% increase** |
| rtL180M/M204I | R | 0.19 ± 0.04 | 0.65 ± 0.08 | ||
| rtL80I/L180M/M204I | R | 0.35 ± 0.01 | 0.34 ± 0.04 | 84% increase* | 48% decrease** |
| PC | 0.46 ± 0.12 | 1.08 ± 0.06 | 0.35 ± 0.04 | ||
| PC/rtL80I | 0.03 ± 0.02 | 0.5 ± 0.06 | 0.04 ± 0.00 | 54% decrease** | 88% decrease** |
| PC/rtM204I | R | 0.28 ± 0.03 | 1.40 ± 0.16 | ||
| PC/rtL80I/M204i | R | 0.70 ± 0.08 | 0.27 ± 0.03 | 150% increase** | 80% decrease** |
| PCrtL180M/M204I | R | 0.32 ± 0.09 | 0.54 ± 0.06 | ||
| PC/rtL80I/L180M/M204I | R | 0.67 ± 0.02 | 3.27 ± 0.38 | 109% increase** | 506% increase** |
a
The wild type is genotype D; PC signifies that the G1896A mutation in the PC region (which prevents HBeAg synthesis) is present.
b
EC50s are means ± standard deviations of the pooled results from three independent assays. R, resistant (i.e., no dose-dependent inhibition of viral replication observed at LMV concentrations up to 10 μM).
c
Relative replication yields are the means ± standard deviations from at least three independent assays.
d
Percent changes in relative replication yield for each pair with and without LMV, with statistically significant differences of P < 0.05 (*) and P < 0.01(**) indicated.