Table 3.
Experimental studies of influenza B virus with NA mutations resulting in decreased susceptibility to FDA-approved NAIs.
| NA mutation and function a |
Method of testing b |
Susceptibility to NAIs (range fold difference) c |
Method of virus generation (drug concentration) d |
Reference | |
|---|---|---|---|---|---|
| Oseltamivir | Zanamivir | ||||
| Catalytic mutation | |||||
| R152K | CL | 252 | 4.7 | RG | Jackson et al., 2005 |
| R292K | CL | >300 | 28.5 | RG | Jackson et al., 2005 |
| Framework mutation | |||||
| E119A | CL | >300 | >560 | RG | Jackson et al., 2005 |
| E119D | FL | 117 | 32667 | Zanamivir (10 μM) | Cheam et al., 2004 |
| E119D | CL | >300 | >560 | RG | Jackson et al., 2005 |
| E119G | P | nd | 86 | Zanamivir (60 μM) | Staschke et al., 1995 Colacino et al., 1997 |
| E119G | FL | nd | 1243 - 1586 | Zanamivir (300 μM) | Barnett et al., 1999 |
| E119G | CL | 31.1 | >560 | RG | Jackson et al., 2005 |
| E119V | CL | >300 | 1.9 | RG | Jackson et al., 2005 |
| D198N | FL | 3.0 - 3.2 | 4.9 - 5.8 | Zanamivir (1μM) | Hatakeyama et al., 2011 |
| I222T | FL | 7.2 | 2.1 | Oseltamivir (1μM) | Hatakeyama et al., 2011 |
a
The function of NA mutation is based on Colman et al. (1989), N2 numbering.
b
Fold difference in mean IC50 values derived from FL, fluorescence-based or CL, chemiluminescence-based assay or P, plaque reduction assay in MDCK cells.
c
Fold difference as compared to mean IC50 value of susceptible isolates.
d
Concentration of drug during passaging which lead to resistant virus.
Abbreviations: nd, no data; RG, reverse genetics.