Bat-Derived Influenza Hemagglutinin H17 Does Not Bind Canonical Avian or Human Receptors and Most Likely Uses a Unique Entry Mechanism

SummaryA new influenza-like virus genome (H17N10) was recently discovered in bats and offers a new perspective about the origin and evolution of influenza viruses. The viral envelope glycoprotein hemagglutinin (HA) is responsible for influenza virus receptor binding, fusion, and entry into the cell; therefore, the structure and function of HA H17 was characterized. The 2.70 Å resolution crystal structure revealed that H17 has a typical influenza A virus HA fold, but with some special features, including a distorted putative sialic acid (SA) binding site and low thermostability. No binding to either the canonical human α2,6 SA-linkage or avian α2,3 SA-linkage receptor was observed. Furthermore, H17 glycan binding was not detected using a chip covering more than 600 glycans. Our results demonstrate that H17 is unique among characterized HAs and that the bat-derived influenza virus may use a different entry mechanism compared to canonical influenza viruses.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Bat influenza H17 lacks canonical human or avian receptor binding capacity ► H17 has a distorted receptor binding site with negatively charged residues ► H17 displayed trypsin susceptibility and instability even at pH 8.0 ► An exposed fusion peptide is observed in H17 structure due to contorted trimerization