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

In conclusion, the three sets of co-expressed transcripts identified in response to VN1203-WT were associated with immune and apoptosis signaling pathways that increased over time, metabolic cellular processes that were largely decreasing, and T cell signaling pathways that exhibited a biphasic pattern. The three sets of proteins capturing the host response dynamics were related to host antiviral defenses, reactive oxygen species observed to increase as infection progressed, and opsonization. Notably, upstream regulators highly enriched in each of the transcript or protein sets were identified (p-value as low as 10 -111 for LPS regulating eigentranscript #2), which confirmed that this method captures groups of co-regulated transcripts/proteins. Importantly, there was an overlap of 29 signaling pathways that were found in both transcript and protein sets, including Role of NFAT in Regulation of the Immune Response, Apoptosis Signaling and Coagulation System, suggesting complementary sensitivity between the transcriptomic and proteomic profiles.