TABLE 2.
Susceptibility to NAIs and viral properties caused by the selected NA substitutions in avian N5 influenza viruses
| Influenza virus NA amino acid change (N2 numbering) | Selection NAIa | NA activity (nM) ± SD | IC50 ± SDb (fold change)c |
Mean infectivity (log10 PFU/ml) ± SD | Mean plaque size (mm) ± SD | Genetic stabilityd (% read) | ||
|---|---|---|---|---|---|---|---|---|
| Oseltamivir | Zanamivir | Peramivir | ||||||
| rgN5 WT | Not applicable | 44,311 ± 405 | 0.55 ± 0.002 (1.0) | 0.17 ± 0.001 (1.0) | 0.05 ± 0.001 (1.0) | 8.6 ± 0.1 | 0.79 ± 0.19 | Not applicable |
| rgN5 L91I | OS | 46,801 ± 913 | 0.59 ± 0.001 (1.1) | 0.20 ± 0.001 (1.1) | 0.05 ± 0.001 (1.1) | 8.8 ± 0.1 | 0.71 ± 0.22 | NDf |
| rgN5 E119V | OS | 13,527 ± 457 | 31.89 ± 0.009 (58.5) | 128.1 ± 0.021 (736.6) | 2.88 ± 0.001 (63.9) | 8.5 ± 0.1 | 0.57 ± 0.18g | V (100) |
| rgN5 N147I | ZA | 36,505 ± 798 | 0.56 ± 0.001 (1.0) | 5.34 ± 0.003 (30.7) | 0.15 ± 0.001 (3.3) | 8.83 ± 0.2 | 0.74 ± 0.21 | I (89), N(11) |
| rgN5 K187R | OS | 48,329 ± 278 | 0.87 ± 0.001 (1.6) | 0.27 ± 0.001 (1.5) | 0.05 ± 0.001 (1.0) | 8.64 ± 0.1 | 0.66 ± 0.14 | ND |
| rgN5 Q221H | OS | 48,749 ± 392 | 0.58 ± 0.001 (1.1) | 0.47 ± 0.001 (2.7) | 0.05 ± 0.001 (1.1) | 8.65 ± 0.1 | 0.71 ± 0.18 | ND |
| rgN5 H274Y | Inducede | 35,023 ± 79 | 589.80 ± 0.061 (1,081.8) | 0.47 ± 0.001 (2.7) | 14.04 ± 0.004 (311.7) | 7.5 ± 0.1g | 0.57 ± 0.10g | Y (98), H (2) |
| rgN5 R292K | Induced | 15,150 ± 545 | 525.40 ± 0.042 (963.7) | 0.68 ± 0.001 (3.9) | 12.78 ± 0.003 (283.7) | 8.4 ± 0.1 | 0.68 ± 0.16 | K (83), R (17) |
| rgN5 L91I+E119V | OS | 9,820 ± 49 | 23.58 ± 0.005 (43.3) | 96.61 ± 0.016 (555.5) | 3.9 ± 0.001 (86.5) | 8.34 ± 0.1 | 0.42 ± 0.13g | I (100), V (100) |
a
The NAI used in the selection of the corresponding mutations.
b
The values are means obtained from two independent experiments.
c
Fold change relative to the mean IC50s of the rgN5-WT virus.
d
Illumina sequencing was used to analyze the sequence variation.
e
The mutant was introduced for comparison.
f
ND, not determined due to insignificant alteration of NAI susceptibility of the indicated mutant virus.
g
P < 0.05 compared with the corresponding infectivity value or plaque size of WT virus.