Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice

Tchitchek, Nicolas; Eisfeld, Amie J; Tisoncik-Go, Jennifer; Josset, Laurence; Gralinski, Lisa E; Bécavin, Christophe; Tilton, Susan C; Webb-Robertson, Bobbie-Jo; Ferris, Martin T; Totura, Allison L; Li, Chengjun; Neumann, Gabriele; Metz, Thomas O; Smith, Richard D; Waters, Katrina M; Baric, Ralph; Kawaoka, Yoshihiro; Katze, Michael G

Finally, the MC and VC profiles associated with VN1203-NS1trunc mutation largely changed at early dpi (1 and 2 dpi). At 1 dpi, these 2 coefficients were higher in the mutant than in the matched dose of the WT, but lower at 2 dpi (Figures 4, and 5D ). This was related to the enhanced, early expression (i.e. at 1 dpi, relative to 2 dpi for all other viruses) of transcripts directly involved in the innate immune response and inflammation (Additional file 6: Figure S3 ), which was also reported previously [31] . It was interesting to find that this behavior was very similar to the CA04 at the highest dose (10 6 PFU). CA04-WT was used as a much lower pathogenicity comparator which confirmed that the main effect of increasing infection dose was to increase the magnitude of the hostresponse (Additional file 7: Figure S4 , and Figure 4 ).