SUMMARYAvian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups. We found two closely related HA sequences in the same duck species in 2010 and 2013. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far remained uncharacterized. We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC-II), which facilitates viral entry. Unlike the broad MHC-II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC-II usage that suggests a limite... More
SUMMARYAvian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups. We found two closely related HA sequences in the same duck species in 2010 and 2013. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far remained uncharacterized. We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC-II), which facilitates viral entry. Unlike the broad MHC-II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC-II usage that suggests a limited host range and zoonotic potential. Using cell lines overexpressing MHC-II, we rescued recombinant H19 IAV. We solved the H19 crystal structure and identified residues within the putative Sia receptor binding site (RBS) that impede Sia-dependent entry.Graphical AbstracteTOC BlurbKarakus et al. uncovers H19 influenza A virus genomes in North Californian ducks. Instead of using the conventional influenza virus receptor sialic acid, H19 uses MHC class II proteins to enter host cells. MHC class II receptor usage of H19 is restricted to certain species suggesting a limited zoonotic potential.
