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

ds (arithmetic means) of the biological conditions and the transcriptomic distances (Euclidean distances) based on the signatures of transcripts associated with the kinetics of the host response to VN1203-WT (Additional file 5: Table S3 , Figure 4 ). MC and VC were calculated only for the transcriptomic data, as we were unable to discriminate proteomic samples at early time-points (1 and 2 dpi), resulting in a lack of sensitivity for the analysis. We first observed that increasing the inoculation dose was related to an increase in magnitude of the host response. Indeed, at each dpi, infection with 10 2 PFU triggered a lower MC compared to 10 3 PFU, while 10 4 PFU triggered the strongest MC. Moreover, different inoculation dosages also resulted in different velocities of the host response changes. With regards to time, the greatest transcriptomic VC difference was found at 2 dpi, followed by the difference quantified between 1 and 2 dpi. With regards to dosage, the lowest transcriptomic VC coefficient difference was found for 10 2 PFU and the greatest transcriptomic VC coefficient difference was found for 10 4 increasing dosages lead to higher magnitude changes of these transcripts/proteins and an increased velocity, especially between 1 and 2 dpi.