Distribution patterns of influenza virus receptors and viral attachment patterns in the respiratory and intestinal tracts of seven avian species

Wild aquatic birds are generally considered to be the source of all influenza viruses found in mammal and avian species, including humans, pigs, horses, minks, marine mammals, cats, and a great number of domestic avian species [1]. Phylogenetic studies indicate that all human influenza viruses, including the predominant strains associated with the seasonal flu (H1, H2, and H3 subtypes) originated from an avian ancestor [2]. More recently, a swine-origin influenza A H1N1 virus (pH1N1), which contains genes of human, avian and swine influenza viruses, caused the first pandemic of the 21st century [3].The host restriction of influenza A viruses is in part determined by specific sialic acid receptors on the surface of susceptible cells. These receptors are composed of nine carbon monosaccharides, usually found on the outermost terminal position of glycan chains, linked to cell-surface glycoproteins and glycolipids [4]. The N-acetylneuraminic acid (Neu5Ac), one of the most common sialic acids, is usually bound to galactose (Gal) in an α-2,3 (Neu5ACα-2,3Gal) or α-2,6 configuration (Neu5ACα-2,6Gal), and their expression and distribution are cell specific [5]. The affinity of influenza viruses for these receptors varies according to the species from which they are isolated. Influenza viruses of avian origin preferentially bind to Neu5Acα-2,3Gal (α-2,3 receptors, avian-like receptors), the form that predominates in the duck enteric tract where these viruses replicate [6,7]; whereas human influenza strains recognize Neu5ACα-2,6Gal (α-2,6 receptors, human-like receptors) [8,9].For many years, it was thought that the inter-species barrier could only be crossed after adaptation of an avian influenza virus in pigs, since pigs were shown to harbor both α-2,3 and α-2,6 receptors [6,10]. Later on, it was observed that the H5 and H7 avian influenza virus subtypes could be directly transmitted from poultry to humans, in spite of having α-2,3 receptor specificity [11-13]. This observat