Glycan Receptor for Influenza Virus

Influenza viruses are found in wide range of animals, including humans, in nature. When avian and human viruses simultaneously infect an intermediate host, such as pigs, genetic recombination can occur between these viruses. There is concern regarding interspecies transmission, both initial animal-to-animal infection and outbreaks of pandemic viruses in the human population. Hemagglutinin (HA) is a trimeric protein expressed on the influenza virus membrane. The globular head domain of the HA contains a receptor-binding site (RBS) that mediates virus attachment to host cells. Sialic acid (SA)-containing glycans, termed sialoglycans expressed on the host cell surface, are considered to serve as influenza virus receptors in both interspecies transmission and epidemics in a specific host. Influenza virus HAs recognize specific linkages of sialic acids in the receptors. Recently, histochemical studies using lectins specific for sialic acid linkages demonstrated that the characteristic distribution of sialoglycans is associated with interspecies viral transmission. To understand interspecies transmission of influenza viruses, it is essential to elucidate the molecular mechanisms of the interaction between influenza virus HAs and sialoglycan receptors expressed on different host cells. This review article focuses on the structure and distribution of receptors for human and other animal influenza viruses, and on molecular mechanisms underlying influenza virus recognition with specific glycan structures. This review also introduces synthetic glycopolymers carrying multivalent sialylated carbohydrates, which have been applied not only to address the molecular mechanisms of virus host cell interaction, but also inhibition of influenza virus infection.