TABLE 3.
Emergence of drug-resistant variants during oseltamivir treatment of BALB/c mice infected with H5N1 influenza viruses
| H5N1 virus | Before oseltamivir treatment (NA mutations)
|
After oseltamivir treatment
|
|||
|---|---|---|---|---|---|
| NA mutations
|
NA enzyme inhibition assay (mean IC50 [nM] ± SE)d
|
||||
| Dominant virus populationa | Individual clone(s) (no. clones/total no. sequenced)b | Dominant virus population (no. of infected mice/total no. of mice)c | Oseltamivir carboxylate | Zanamivir | |
| Human | |||||
| A/Thailand/1(Kan-1)/04 | None | None | None (3/3) | 0.2 ± 0.1 | 1.4 ± 0.1 |
| A/Turkey/65-1242/06 | None | E119A (2/21), I117V (6/21) | E119A (1/3) | 136.9 ± 8.3 | 1,659.0 ± 441.9 |
| Avian | |||||
| A/chicken/Jogjakarta/BBVET/IX/04 | None | None | None (3/3) | 3.7 ± 1.5 | 0.8 ± 0.1 |
| A/whooper swan/Mongolia/244/05 | None | None | None (3/3) | 1.2 ± 0.4 | 0.7 ± 0.1 |
| A/duck/Laos/25/06 | None | I222M (2/22) | None (3/3) | 0.1 ± 0.1 | 0.6 ± 0.1 |
a
RNA was isolated directly from virus-containing allantoic fluid used as an inoculum.
b
TOPO TA cloning was performed by using PCR products obtained by amplification of the virus inoculum. Individual virus clones were analyzed by sequencing. Amino acid numbering is based on N2 NA (19).
c
RNA was isolated directly from lung homogenates of three mice on day 9 p.i.
d
Values are means from three independent experiments.