TABLE 3.
NA inhibitor susceptibilities of recombinant viruses
| Recombinant virus and NA mutationa | Relative NA activity (%)e | Oseltamivir
|
Zanamivir
|
Peramivir
|
|||
|---|---|---|---|---|---|---|---|
| Mean IC50 ± SD (nM)f | Fold change | Mean IC50 ± SD (nM)f | Fold change | Mean IC50 ± SD (nM)f | Fold change | ||
| Laos/26 H5N1 NAb | |||||||
| Wild type | 100 | 0.8 ± 0.2 | 1 | 0.5 ± 0.1 | 1 | 0.3 ± 0.02 | 1 |
| I222M | 76 ± 12 | 27.8 ± 4.2 | 36 | 0.5 ± 0.1 | 1 | 0.3 ± 0.02 | 1 |
| H274Y | 43 ± 16 | 695.6 ± 178.0 | 911 | 0.6 ± 0.1 | 1 | 142.4 ± 31.4 | 533 |
| I222M + H274Y | 52 ± 4 | 6,126.2 ± 1,319.0 | 8,024 | 1.4 ± 0.1 | 3 | 891.4 ± 119.9 | 3,340 |
| I222V | 71 ± 9 | 5.3 ± 1.5 | 7 | 0.7 ± 0.1 | 1 | 0.3 ± 0.04 | 1 |
| I222V + H274Y | 29 ± 6 | 1,469.7 ± 291.3 | 1,925 | 1.1 ± 0.1 | 2 | 562.1 ± 66.2 | 2,106 |
| E119G | 1 ± 1 | 3.1 ± 0.6 | 4 | 677.3 ± 187.8 | 1,345 | 43.6 ± 2.0 | 164 |
| Vn/1203 H5N1 NAc | |||||||
| Wild type | 100 | 0.2 ± 0.02 | 1 | 0.6 ± 0.1 | 1 | 0.3 ± 0.02 | 1 |
| H274Y | 74 ± 15 | 498.9 ± 81.9 | 2,502 | 1.0 ± 0.2 | 2 | 27.0 ± 3.8 | 108 |
| D198G | 50 ± 7 | 6.4 ± 0.6 | 32 | 25.5 ± 3.9 | 44 | 1.0 ± 0.1 | 4 |
| E119G | 2 ± 1 | 0.7 ± 0.1 | 3 | 868.1 ± 365.2 | 1,485 | 3.0 ± 0.5 | 12 |
| NC/20 H1N1 NAd | |||||||
| Wild type | 100 | 1.5 ± 0.2 | 1 | 0.7 ± 0.1 | 1 | 0.2 ± 0.1 | 1 |
| I222M | 67 ± 12 | 11.9 ± 1.7 | 8 | 0.4 ± 0.1 | 1 | 0.2 ± 0.1 | 1 |
| H274Y | 56 ± 1 | 1,178.3 ± 164.1 | 761 | 0.8 ± 0.2 | 1 | 82.8 ± 19.7 | 347 |
| I222M + H274Y | 50 ± 2 | 3,009.1 ± 395.2 | 1,943 | 0.5 ± 0.1 | 1 | 95.5 ± 25.7 | 400 |
| I222V | 141 ± 25 | 4.5 ± 0.9 | 3 | 1.3 ± 0.3 | 2 | 0.3 ± 0.02 | 1 |
| I222V + H274Y | 123 ± 10 | 1,502.8 ± 216.0 | 971 | 1.5 ± 0.3 | 2 | 213.0 ± 46.1 | 893 |
Recombinant viruses were generated using reverse genetics in which the NA gene was derived as indicated and the remaining seven genes were derived from A/PR/8/34. Mutations were generated in the NA gene by site-directed mutagenesis.
The NA gene was derived from A(H5N1) virus A/Chicken/Laos/26/2006.
The NA gene was derived from A/Vietnam/1203/2004.
The NA gene was derived from the A(H1N1) virus A/New Caledonia/20/99.
The mean ± standard deviation for the relative NA activity compared with that of the respective wild-type virus, which was considered 100%.
The mean IC50 values and standard deviations were based on the analysis of reverse genetics-rescued viruses with oseltamivir, zanamivir, and peramivir in three separate assays.