The first part of the talk will describe the human metapneumovirus (HMPV) fusion (F) as a key viral surface glycoprotein that is essential for target-cell recognition, attachment, and entry. Heparan sulfate proteoglycans extensively decorate the human cell surface and were previously described as an important cellular receptor for HMPV F, underlining the role of glycans as viral attachment factors. For the first time, we will describe the glyco-interactome of the HMPV fusion protein. HMPV F binding to glycan structures was first identified by glycan array using a library that broadly represents the human lung glycome. The novel glycan-HMPV F interactions were further confirmed by surface plasmon resonance. Lastly, the identified oligosaccharides were evaluated for their potency to compete with the cellular receptors using an in vitro HMPV cellular binding inhibition assay. We demonstrate that these glycans have the potential to compete with the cellular receptors used for HMPV entry and consequently block HMPV infection. Saturation transfer difference nuclear magnetic resonance spectroscopy experiments confirmed glycan binding to whole HMPV particles.
The second part will describe the key enzyme UDP-glucose pyrophosphorylase (UGP), which produces UDP-glucose as an essential precursor for the synthesis of complex carbohydrates and glycoconjugates, including the virulence factor lipopolysaccharide (LPS). UGP-deficient strains of the opportunistic pathogen Pseudomonas aeruginosa (Pa) have truncated LPS, making them more sensitive towards innate immune factors and less virulent in animal models of acute infection. To define PaUGP as a potential drug target, we aimed to (a) confirm its contribution to virulence in human-relevant infection models and (b) reveal structural and functional features of the enzyme that could serve as points for selective inhibition. Specifically, we aimed to explore the link between PaUGP activity and its oligomeric state.