Influenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 infections of mice

Two different influenza A viruses showing no pathogenicity towards the laboratory mouse were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a similar 50% mouse lethal dose and the same peak lung concentration, they elicited dramatically different pathological signatures and ARDS courses. In the absence of any virus labeling, a histologist unaware of which infection he was looking at could readily distinguish infections caused by these two viruses. This suggests that fatal infections caused by different highly virulent influenza A viruses do not necessarily share the same pathogenesis. The different histological pictures shown here refute the hypothesis of a single, universal “cytokine storm” underlying all fatal influenzal diseases. Research is thus crucially needed to identify underlying sets of virulence markers and to examine whether it might be advantageous to tailor treatment to the influenza virus pathotype.