The burden of infection with seasonal influenza viruses is significant. Each year is typically characterised by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually and whilst this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences and variation in clinical assessment are also important. To improve our understanding of the impact of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding and expression of cytokines, chemokines and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2) or influenza B viruses. Gene expression was also assessed in the lower respiratory tract (LRT). Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses and peak expression of IL1α, IL1β, IL6, IL12p40, IFNα, IFNβ and TNFα mRNAs correlated with peak levels of viral shedding. MCP1 and IFNγ were expressed after the virus peak. Granzymes A and B and IL10 reached peak expression as virus cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations of URT, but were delayed by two-three days, as was virus replication. These data indicate that disease and localised immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and the impact of seasonal influenza.

IMPORTANCE:

Both influenza A and B viruses co-circulate in the human population and annual influenza seasons are typically dominated by an influenza A subtype or an influenza B lineage. Surveillance data indicates that the burden of disease is higher in some seasons, yet it is unclear whether this is due to specific virus strains or to other factors, such as cross reactive immunity or clinical definitions of influenza. We directly compared disease and the localised inflammatory response to different seasonal influenza strains, including the 2009 pandemic strain, in healthy na?ve ferrets. We have found that disease, as well as the cytokine and chemokine responses, were similar irrespective of the seasonal strain or the location of the infection in the respiratory tract. This suggests that factors other than the immune response to a particular virus (sub)type contribute to the variable impact of influenza infection in a population.