Table 3. Viruses containing polymerase acidic amino acid substitutions that showed reduced baloxavir susceptibility, United States, 2016/17 and 2017/18 influenza seasons.
| Type/subtype | Virus name | Codona | PA AA | HINT | FRA | |||
|---|---|---|---|---|---|---|---|---|
| EC50, nM Mean ± SDb |
Fold change to controlc | Fold change to mediand | EC50, nM Averagee |
Fold change to control | ||||
| A(H3N2) | A/Louisiana/50/2017 | ATA | I38 | 1.33 ± 0.22 | 1 | 2 | 1.12 | 1 |
| A/Louisiana/49/2017 | ATG | I38M | 13.88 ± 2.25 | 10 | 17 | 11.75 | 11 | |
| A(H1N1)pdm09 | A/Kentucky/13/2018 | GAA | E23 | 2.39 ± 1.58 | 1 | 2 | NT | NT |
| A/Florida/20/2018 | GGA | E23G | 8.86 ± 1.62 | 4 | 6 | NT | NT | |
| A/Texas/121/2018 | GAA | E23 | 1.90 ± 0.43 | 1 | 1 | NT | NT | |
| A/Arizona/35/2018 | GGA | E23G | 10.24 ± 2.78 | 5 | 7 | NT | NT | |
| A/Illinois/08/2018 | ATA | I38 | 1.61 ± 0.22 | 1 | 1 | 2.12 | 1 | |
| A/Illinois/37/2018 | CTA | I38L | 13.50 ± 3.04 | 8 | 9 | 14.96 | 7 | |
| A/Illinois/38/2018 | CTA | I38L | 12.95 ± 1.87 | 8 | 8 | NT | NT | |
AA: amino acid; FRA: focus reduction assay; HINT: high-content imaging neutralization test; NT: not tested; PA: polymerase acidic; SD: standard deviation.
a Underlined base indicates the nt change.
b Mean and SD of ≥ three independent tests.
c Fold change to EC50 of test virus compared with sequence-matched control virus. A/Texas/121/2018 and A/Arizona/35/2018 also contained E688G and E126D in PA, respectively.
d Fold change to EC50 of test virus compared with baseline median values: 0.80 for A(H3N2) and 1.57 for A(H1N1)pdm09 (Table 4).
e Average of two results.
An arbitrary threshold (˃ three-fold EC50) was used to report PA amino acid substitutions that confer reduced susceptibility to baloxavir.