Epidemic influenza virus strains with high growth capability induce severe inflammatory response in vivo

Influenza epidemics occur worldwide and impose a substantial socioeconomic burden. In our previous studies, epidemic influenza virus strains isolated from seasonal influenza patient specimens exhibited a wide range of growth capabilities and demonstrated growth-dependent cell death in vitro. Based on these findings, we hypothesized that diversity in growth capabilities contributes to the severity of influenza infection. In this study, we investigated the relationship between the growth capabilities of epidemic influenza virus strains and the severity of inflammation in the bronchoalveolar cavity of inoculated mice. Our results demonstrated that high growth capability influenza A virus (IAV) strains replicated significantly faster in mice compared to low growth capability strains. High growth capability strains also induced earlier and stronger production of pro-inflammatory cytokines and promoted more rapid infiltration of inflammatory cells into the lungs. Moreover, mice infected with high growth capability strains exhibited greater weight loss and a higher mortality than those infected with low growth capability strains. These findings suggest that high growth capability IAV strains circulating in the community may induce rapid and pronounced inflammatory responses in infected individuals, leading to severe illness. Our findings may facilitate the identification of high-risk strains and support the development of improved therapeutic strategies for severe influenza cases, thereby providing new insights into the mechanisms underlying influenza severity.