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The species-specific signatures of the swine-origin influenza A (H1N1) virus (S-OIV), which caused the current influenza pandemic, have not been well defined. By comparing the protein sequences of S-OIVs with those of swine, avian and human influenza viruses, we found that that almost all human IAVs and those causing influenza pandemics, including the 2009 S-OIVs, had a combination of glutamic acid (E) residue at position 14 and phenylalanine (F) residue at position 55 in their M2 protein, while only 22% and 4% of the swine and avian IAVs had the E14-F55 combination. These finding suggests that E14-F55 combination in the M2 protein of S-OIV may be a molecular determinant associated with its human-to-human transmission.

E14-F55 combination in M2 protein: a putative molecular determinant responsible for swine-origin influenza A virus transmission in humans