Abstract
Characterization of host adaptation markers among human isolates is important for recognizing the potential for cross-species transmission in avian influenza A viruses. Here, we studied two new potential adaptive mutations, V292I and D740A, in the PB2 protein that were identified by a multi-factor regression model. The study shows that the prevalence of the PB2-V292I mutation is increased in H7N9 influenza viruses isolated from both humans and birds over the past 6 years. The phylogenetic tree showed that influenza A/H7N9 has a lineage based on the strains containing PB2-292I. Polymerase complexes containing PB2-292I/627K derived from H7N9 exhibit increased polymerase activity. PB2-292I coupled with 627K also enhances viral transcription and replication in cells, whereas PB2-292I alone did not show the same effect in the H7N9 virus. However, PB2-740A only had a limited prevalence in 2013, and the change from D to A in PB2-740A may have a negative effect on the replication of the H7N9 virus in cells.