Replication levels of the wild-type subgenomic replicon, a replication deficient mutant (GND), mutants containing the rare escape mutations alone (R2937G, upper panel; R2937G/I2940T, middle panel; R2937S, lower panel), or in combination with mutations at position 2875 and/or 2881 were compared. Replication of the wild-type was set 100%. Means and standard errors of three individual experiments are shown. P values comparing replication of mutants and wild-type were calculated by paired t test and are indicated as follows: * P<0.05, ** P<0.005, and *** P<0.0005.