Influenza A Strain-Dependent Pathogenesis in Fatal H1N1 and H5N1 Subtype Infections of Mice

摘要

To determine if fatal infections caused by different high-ly virulent in. uenza A viruses share the same pathogenesis, we compared 2 different in. uenza A virus subtypes, H1N1 and H5N1. The subtypes, which had shown no pathoge-nicity in laboratory mice, 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, each had a distinct pathologic signature and caused a different course of acute respiratory distress syndrome. In the absence of any virus labeling, a histologist could readily distinguish in-fections caused by these 2 viruses. The different histologic features described in this study here refute the hypothesis of a single, universal cytokine storm underlying all fatal in. u-enza diseases. Research is thus crucially needed to identify sets of virulence markers and to examine whether treatment should be tailored to the in. uenza virus pathotype