Influenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A/Brevig Mission/1/1918, A/California/4/09) and two seasonal (A/New Caledonia/20/99, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF?B following infection with A/New Caledonia/20/99 and a unique cluster of genes expressed following infection with A/Brevig Mission/1/1918. A common anti-viral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza infection. Comparison of the global response to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss.
Continuously evolving influenza viruses present a global threat to human health however, these host responses display strain-dependent differences that are incompletely understood. Thus we conducted a detailed comparative study comparing the immune response of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common, but also strain specific, features. Among the stain specific elements were a time shift of the ISG response, selective induction of NF?B signaling by one of the seasonal strains and massive RNA degradation as early as 4 hours post-infection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects that characterize the distinct differences in the immune response to pandemic or seasonal influenza viruses.