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

To determine whether the VC and MC were related to disease outcome and viral pathogenicity, we performed a correlation analysis between these coefficients and the phenotypic variables. All biological conditions were considered together in these analyses to assess the correlations with a large significance. For each biological condition, we determined the mean body weight of the animals, viral titer, viral messenger RNA and viral genomic RNA measurements in the lung, and calculated the difference between the means of any two consecutive time-points for viral titer (Δ mean viral titer), viral RNA (Δ mean viral Table S3 . A significant association was found between MC and mean body weight (Spearman's rho = −0.7984), suggesting that the magnitude of host response is significantly associated with morbidity ( Figure 6A ). The VC was not significantly associated with any criteria when considering phenotypic variables within a given time-point; however, the VC was significantly associated with Δ mean viral titer (Spearman's rho= 0.8459, Figure 6B ), Δ mean viral mRNA (rho =0.8544), and Δ mean viral gRNA (rho =0.8426) at the previous time-point. This suggests that the velocity of the host response can be predicted by changes in viral replication at the preceding time-point.