The role of receptor binding specificity in interspecies transmission of influenza viruses

Abstract

Influenza A virus infection begins with the binding of the hemagglutinin (HA) glycoprotein to sialic acid-containing receptors on the surface of the target cell. Avian influenza viruses, including avian H5N1, H7, and H9N2 viruses, can occasionally cross the species barrier and infect humans; however, these viruses do not spread efficiently from person to person, perhaps, partly, owing to differences in the receptor-binding specificities of human and avian influenza viruses. The HAs of avian influenza viruses must adapt to receptors in humans to acquire efficient human-to-human transmissibility. In this review, we discuss the receptor binding specificity of influenza A viruses and its role in interspecies transmission.

Figure 1. The receptor-binding properties of influenza A viruses

a, The HA of human isolates preferentially recognizes sialic acid linked to galactose by α2,6-linkages (Siaα2,6Gal), whereas the HA of avian isolates preferentially recognizes sialic acid linked to galactose by α2,3-linkages (Siaα2,3Gal). b, Binding of influenza A viruses to human respiratory tissues. A human virus and an avian virus were incubated with human trachea tissue sections and then stained with appropriate antibodies. All sections were subsequently incubated with fluorescent-labeled secondary antibodies and Hoechst dye (blue). The green stain indicates virus binding.

Figure 2. Structural model of H5N1 virus HA in complex with human receptor analogs

Left panel, the monomer of A/Vietnam/1203/2004 HA [Protein Data Bank (PDB) accession 2FK0]. Right panel, close-up view of the globular head of A/Vietnam/1203/2004 HA. The human receptor analog [derived from its complex with H9 HA (PDB accession 1JSI)] is docked into the structure (shown in red). Images were created with MacPymol [http://www.pymol.org/].