Influenza A viruses are further classified into subtypes, based on the combinations of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). The primary natural reservoir for most influenza A subtypes are wild aquatic birds; however, through a series of mutations, a small subset of these viruses have adapted for infection of humans (and other animals). A key determinant of whether a particular influenza A subtype can infect humans is its binding specificity. Avian influenza A preferentially binds to cell surface receptors with a terminal α2,3‐linked sialic acid, while human influenza A preferentially binds to cell surface receptors with a terminal α2,6‐linked sialic acid. Via mutation, some avian influenza A viruses have successfully altered their binding specificity from α2,3‐ to α2,6‐linked sialic acid. However, in order to emerge in humans, avian influenza A viruses must also adapt their RNA polymerases for function in mammalian cells, as well as mutating for stability in the acidic respiratory tract of humans.