Mouse-adapted virus MA9-22 has restored fitness in DBA/2J mice. Groups of 5 DBA/2 mice were intranasally inoculated with 30 μl PBS containing 750 PFU of virus. (A and B) Body weight changes (A) and survival (B) were observed for 14 days in intact mice. (C) Virus tissue titers in nasal turbinates, trachea, and lungs were measured 4 dpi. (D) Noninvasive bioluminescence intensities in the lungs were observed for 4 days in intact mice. The ratio of bioluminescence/titer at 4 d.p.i. was calculated for the four mouse-adapted (MA) variants. In all panels, the reported values are means ± standard deviations (n = 5) and symbols are PBS (white circles), WT (black circles), MA-9 (pink squares), MA9-1 (brown circles), MA9-2 (yellow triangles), MA9-15 (orange diamonds), and MA9-22 (blue triangles). ***, P < 0.001.