Sialyl sugar chains as receptors and determinants of host range of influenza A viruses

Sialic acids (SA) in host cell receptors are widely distributed in animals; however, the molecular species and the sialyl linkages vary among animal species. Previous studies have shown that the sialyllacto/sialylneolacto-series sugar chains, SAα2–3(6)Galβ1–3(4)GlcNAcβ1-, in glycoproteins and glycolipids are the functional receptor sugar chains for influenza A and B viruses from humans and animals. Amino acid substitutions in hemagglutinin (HA), the glycoprotein responsible for receptor binding of influenza viruses, have resulted in changing receptor specificity for the molecular species (Neu5Ac, Neu5Gc) as well as sialyl linkage (SA2–3Gal, SA2–6Gal). The host range is influenced by host cell receptors; the Neu5Gc2–3Gal moiety present on crypt epithelial cells of duck colon has been shown to play an important role in the enterotropism of avian influenza viruses. In addition, a virus with an HA recognizing the Neu5Ac2–6Gal but not Neu5Ac2–3Gal or Neu5Gc2–3Gal, failed to replicate in horses, while one with an HA recognizing the Neu5Gc2–3Gal moiety replicated in horses. The abundance of the Neu5Gc2–3Gal moiety in epithelial cells of horse trachea supports that recognition of this moiety is critical for viral replication in horses. Thus, substantial evidence suggests the significance of the molecular species and linkage in the host range of the influenza. Here we report the biological role of receptor sialyl sugar chains in host range determination of influenza A viruses.