Complex reassortment of polymerase genes in Asian influenza A virus H7 and H9 subtypes

- Multiple direct and/or indirect reassortments may occur between H7 and H9 polymerase genes.
- H1N1pdm09-like PA gene may play an important role in recent human H7N9 pandemic.
- Polymerase reassortment between H7N9 and H9N2 is still ongoing in South China.
- New epidemic in South China was caused by novel H7N9 with newly adapted polymerase.

The epidemic first caused by a novel H7N9 avian influenza A virus (IAV) has emerged in China recently. Meanwhile, a novel H7N7 IAV with the ability to infect mammals was also found in China. Both IAVs of H7 subtype possess internal genes originating from H9N2. As internal polymerase genes play a key role for interspecies transmission of IAVs, it is important to trace the reassortment history of polymerase genes in the IAVs of H7 and H9 subtypes. Here, by comprehensive phylogenetic analyses of Asian H7 and H9 polymerases, we showed a significant incongruence among the tree topologies of polymerase genes PA, PB1 and PB2, which suggested frequent intra-subtype reassortments in the IAVs of H9N2. Moreover, the PA gene of H1N1pdm09 clustered with that of H9N2 located at the basal position of clade A, including most strains isolated from mammals and the recent novel H7N9 in the phylogenetic tree of PA. This finding indicated that the H1N1pdm09-like PA gene may play an important role in the human H7N9 epidemic. Results also showed that the earlier strains of H7 subtype were divided into several clusters dispersed within the strains of H9N2, implying multiple direct and/or indirect reassortments may occur between H7 and H9 polymerase genes. Furthermore, the most recent reassortments occurred multiply on the polymerase genes of the newly emerging H7N9 isolated from human in South China, evolving E627K mutation in PB2 independently. These results suggest that the reassortment history of polymerase genes in Asian IAVs of H7 and H9 subtypes is complex and timely evolutionary analyses on the novel H7N9 with newly adapted polymerase are necessary for preventing a potential outbreak in South China.