complex is highly error-prone, like HIV-1 RT, then this may cause the excessive production of unwanted genomic mutations, ultimately leading to catastrophic mutagenesis. Thus, it can be hypothesized that the high enzyme fidelity nature of IAV Pol complex which was observed in this study may enable the viruses to avoid this lethal hypermutagenesis. However, even with high enzyme fidelity, the multiple amplification replication strategy may allow the IAV to produce genomic mutations sufficient for viral evolution and host adaptation. The similar reasoning of the high fidelity viral RNA polymerases envisioned above for IAV Pol can be applied to polioviruses which also amplify their RNA genomes multiple times per infection solely by their own high fidelity RNA polymerase. In addition, it was demonstrated that the elevation of genomic mutation rates of poliovirus, which is promoted by an antiviral agent (ribavirin), results in the catastrophic mutagenesis [41,43], supporting the notion that poliovirus is vulnerable to hyper- mutagenesis, and thus their polymerase fidelity might have evolved to be a faithful RNA polymerase. Therefore, since IAV has similar genome replication strategy with poliovirus, a similar mechanistic relationship between the high fidelity nature of the IAV Pol complex and viral high genetic and evolutionary potentials can be applied to influenza A virus. It is also important to address other potential cellular events that may generate IAV genomic mutations during viral life cycle. One References 1. Bragstad K, Nielsen LP, Fomsgaard A (2008) The evolution of human influenza A viruses from 1999 to 2006: a complete genome study. Virol J 5: 40. 2. Ito T, Goto H, Yamamoto E, Tanaka H, Takeuchi M, et al. 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