TABLE 1.
CsA sensitivities of serially passaged and engineered CsA-resistant viruses
| Virus | EC50 | Fold resistanceb | Remarks |
|---|---|---|---|
| Wild-type EAV control | |||
| EAVwt | 2.4 ± 0.5 | 1.0 | |
| 2.1 ± 0.2 | 1.0 | ||
| rEAVwt | 1.6 ± 0.1 | 1.0 | |
| EAV CsA-1 | |||
| Passage 7 virus | ∼10.9a | 5.1 | |
| rEAV nsp5Q21R | 4.4 ± 0.2 | 2.9 | |
| rEAV nsp5Y113H | 4.4 ± 0.3 | 2.8 | |
| rEAV nsp5A134V | 4.5 ± 0.3 | 2.9 | |
| rEAV nsp5Y113H+A134V | 9.1 ± 0.6 | 5.9 | Acquisition of second site reversion nsp5 Q21R or Q21H |
| rEAV nsp5Q21R+Y113H+A134V (rEAVQYA) | 7.2 ± 0.7 | 4.7 | |
| EAV CsA-2 | |||
| Passage 7 virus | ∼11.0a | 5.2 | |
| rEAVA43G | 1.8 ± 0.1 | 1.2 | |
| rEAV nsp5Y113H | 4.4 ± 0.3 | 2.8 | |
| rEAV nsp10Y387H | 1.6 ± 0.1 | 1.1 | |
| rEAVA43G + nsp5Y113H + nsp10Y387H | 4.6 ± 0.3 | 3.0 | |
| EAV CsA-3 | |||
| Passage 7 virus | ∼10.2a | 4.8 | |
| rEAV nsp2A199T | 1.7 ± 0.1 | 1.1 | |
| rEAV nsp5L8S | 2.2 ± 0.1 | 1.4 | Reversion to wt nsp5-L8 |
| rEAV nsp5Q21R | 4.4 ± 0.2 | 2.9 | |
| rEAV nsp5L8S+Q21R | 9.1 ± 1.4 | 5.9 | Reversion to wt nsp5-L8 |
| rEAV nsp2A199T + nsp5L8S+Q21R | 8.7 ± 0.5 | 5.6 | Reversion to wt nsp5-L8 |
a
The EC50 is an estimated value (labeled “ambiguous” during GraphPad data analysis), due to the fact that the EC50 approached the CC50 for CsA in Huh7 cells, leaving only a few data points between the two values.
b
Fold resistance of the P7 viruses relative to EAVwt; for the engineered rEAV ALV mutants, fold resistance was calculated relative to the rEAVwt value.