Genomic Signatures of Influenza A Pandemic (H1N1) 2009 Virus

Adaptive mutations that have contributed to the emergence of influenza A pandemic (H1N1) 2009 virus, which can replicate and transmit among humans, remain unknown. We conducted a large-scale scanning of influenza protein sequences and identified amino acid–conserving positions that are specific to host species, called signatures. Of 47 signatures that separate avian viruses from human viruses by their nonglycoproteins, 8 were human-like in the pandemic (H1N1) 2009 virus. Close examination of their amino acid residues in the recent ancestral swine viruses of pandemic (H1N1) 2009 virus showed that 7 had already transitioned to human-like residues and only PA 356 retained an avian-like K; in pandemic (H1N1) 2009 virus, this residue changed into a human-like R. Signatures that separate swine viruses from human viruses were also present. Continuous monitoring of these signatures in nonhuman species will help with influenza surveillance and with evaluation of the likelihood of further adaptation to humans.