Virulence of pandemic (H1N1) 2009 influenza A polymerase reassortant viruses.

Infections due to the pandemic (H1N1) 2009 influenza A viruses have been considerably mild relative to previous pandemics. However, its continued circulation among human and animal populations heightened concerns for the generation of virulent variants with greater threat to public health. Thus, we explored the potential role of the influenza viral polymerases, including known molecular markers, in altering the virulence phenotype of the 2009 pandemic A/California/04/09 (CA04, H1N1) virus. By examining in vitro polymerase activities and in vivo pathogenicities in mice model, we were able to show that individual or simultaneous expression of virulence factors in PB2, PB1, and PA might not significantly elevate pathogenicity. Nevertheless, we demonstrated that PB2(627K) or PA(97I) derived from different genetic backgrounds and other unknown polymerase markers have the potential to enhance virulence of CA04. Virus rescue and replication studies identified PA as a critical factor in maintaining genetic stability of the CA04 (H1N1) virus.