Influenza A virus plasticity-A temporal analysis of species-associated genomic signatures

Background/purpose: An influenza A pandemic occurred in 2009-2010. A novel H1N1 virus (hereafter H1N1pdm) was responsible for this outbreak. H1N1pdm viruses have been largely seen in recent human influenza A viruses. This virus was descended from a triple-reassorted swine virus consisting of human, avian, and swine origins. As a result, the previously established species-associated signatures could be in jeopardy. Methods: We analyzed all influenza A sequences in the past 5 years after the inclusion of H1N1pdm into human viruses since 2009, and examined how human signatures may lose their distinctness by mixing with avian residues that H1N1pdm have brought in. In particular, we compared how those signatures were changed/shifted in the past 5 years for human-isolated avian influenza A viruses and discussed their implications. Results: Only eight out of 47 signatures remained human-like for human influenza A viruses in the past 5 years. They are PB2 271A; PB1 336I; PA 356R and 409N; NP 33I, 305K, and 357K; and NS1 227R. Although most avian-like residues were preserved in human-isolated avian influenza A viruses, a number of them were found to have become or on the verge of becoming human-like, including PB2 627, PA 100, 356, 404, 409, NP 33, 61, 305, 357, M2 20, and NS1 81. Conclusion: Analyzing how species-associated signatures are becoming human-like in human-isolated avian influenza A viruses helps in assessing their potential to go pandemic as well as providing insights into host adaptation.