Impact of amino acid mutations in PB2, PB1-F2, and NS1 on the replication and pathogenicity of pandemic (H1N1) 2009 influenza viruses

Here, we assessed the effects of PB1-F2 and NS1 mutations known to increase the pathogenicity of influenza viruses on the replication and pathogenicity in mice of pandemic (H1N1) 2009 influenza viruses. We also characterized viruses possessing a PB1-F2 mutation that was recently identified in pandemic (H1N1) 2009 influenza virus isolates, with and without simultaneous mutations in PB2 and NS1. Our results suggest that some NS1 mutations and the newly identified PB1-F2 mutation have the potential to increase the replication and/or pathogenicity of pandemic (H1N1) 2009 influenza viruses. Although the pandemic (H1N1) 2009 influenza A viruses that emerged in the early spring of 2009 circulate widely (4), most infected individuals experience an uncomplicated upper respiratory disorder. These clinical manifestations indicate that the pathogenicity of the pandemic (H1N1) 2009 viruses in most humans is relatively mild, possibly due to preexisting cross-reactive immunity as exemplified by an appreciable im-mune response upon a single vaccination (7, 20, 28). Never-theless, these viruses are clearly more pathogenic than sea