Homologous recombination as an evolutionary force in the avian influenza A virus

Avian influenza A viruses (AIVs), including the H5N1, H9N2, and H7N7 subtypes, have been directly transmitted to humans, raising concerns over the possibility of a new influenza pandemic. To prevent a future avian influenza pandemic, it is very important to fully understand the molecular basis driving the change in AIV virulence and host tropism. Although virulent variants of other viruses have been generated by homologous recombination, the occurrence of homologous recombination within AIV segments is controversial and far from proven. This study reports three circulating H9N2 AIVs with similar mosaic PA genes descended from H9N2 and H5N1. Additionally, many homologous recombinants are also found deposited in GenBank. Recombination events can occur in PB2, PB1, PA, HA, and NP segments and between lineages of the same/different serotype. These results collectively demonstrate that intragenic recombination plays a role in driving the evolution of AIVs, potentially resulting in effects on AIV virulence and host tropism changes.