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

The emergent properties of a biological system are dynamic and best comprehended by examining the system through the sum of its individual components [43] . Through a systems biology approach, we have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis. Magnitude and velocity represent emergent properties of the system that are best captured using an expanded time-course, multiple doses and more than one mutant virus. Therefore, changes in gene expression induced by wild-type and mutant virus are not necessarily specific to a particular mutation, but rather encompass kinetic changes where increasing viral dosage is found to proportionally increase the Magnitude Coefficient and impact the timing of peak Velocity Coefficient during infection. Knowledge of the timing of host response changes will have important implications for treatment administration, particularly early in infection.