Receptor affinity and host range of H16 subtype AIVs

Influenza viruses are a constant threat to animal and human health. While most avian influenza virus (AIV) subtypes infect ducks, a few rare subtypes, such as the H16 subtype, are found almost exclusively in gulls. This unusual host restriction raises an important question: what makes gulls, but not ducks, susceptible to these viruses? Understanding this could help predict how influenza viruses adapt to new hosts, including mammalian species. Influenza viruses attach to cells using a surface protein called hemagglutinin (HA), which binds to specific sugar molecules, called receptors, on the host cell surface. These interactions determine which species a virus can infect. The H16 subtype of AIV appears to have a unique HA structure that limits its ability to recognize the common receptors found in ducks, while efficiently binding to those in gulls. However, the molecular details behind this specificity remain unknown. This project will investigate how H16 viruses recognize and attach to host cells, using a combination of structural biology, molecular analysis, and cell-based experiments. Researchers will compare the HA structures of different H16 viruses and test how strongly they bind to various synthetic receptors using glycan arrays. The project will also examine receptor distribution in gull and duck tissues and analyze the enzymes that produce these receptors. Finally, live virus assays will test how efficiently H16 viruses replicate in gull- and duck-derived cells. By combining molecular, structural, and virological approaches, this research will reveal why H16 viruses are restricted to gulls and what molecular changes would be required for them to infect other bird species, or even mammals. Beyond improving our understanding of influenza ecology, these findings will support better surveillance and early detection of virus strains that could cross species barriers. This project therefore contributes not only to basic virological knowledge but also to global efforts in pandemic preparedness by investigating how influenza viruses may adapt to new hosts in nature.