H19 influenza A virus exhibits species-specific MHC class II receptor usage

• Published in: Cell host & microbe Vol. 32; no. 7; pp. 1089 - 1102.e10
• Main Authors: Karakus, Umut, Mena, Ignacio, Kottur, Jithesh, El Zahed, Sara S., Seoane, Rocío, Yildiz, Soner, Chen, Leanne, Plancarte, Magdalena, Lindsay, LeAnn, Halpin, Rebecca, Stockwell, Timothy B., Wentworth, David E., Boons, Geert-Jan, Krammer, Florian, Stertz, Silke, Boyce, Walter, de Vries, Robert P., Aggarwal, Aneel K., García-Sastre, Adolfo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.07.2024
• Subjects: Animals; avian influenza virus surveillance; Binding Sites; Cell Line; Crystallography, X-Ray; Ducks - virology; entry receptor; glycan array; HA structure; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; hemagglutinin subtype H19; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; host range; Host Specificity; Humans; influenza A virus; Influenza A virus - genetics; Influenza A virus - immunology; Influenza in Birds - virology; MHC class II; N-Acetylneuraminic Acid - metabolism; Phylogeny; Protein Binding; receptor binding site; Receptors, Virus - genetics; Receptors, Virus - metabolism; recombinant H19 influenza A virus; Species Specificity; Virus Internalization; receptor binding site; recombinant H19 influenza A virus; MHC class II; glycan array; avian influenza virus surveillance; entry receptor; host range; influenza A virus; hemagglutinin subtype H19; HA structure
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2024.05.018

Avian 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 has 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 class II), which facilitates viral entry. Unlike the broad MHC class II specificity of H17 and H18 from bat IAV, H19 exhibits a species-specific MHC class II usage that suggests a limited host range and zoonotic potential. Using cell lines overexpressing MHC class 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. [Display omitted] •Influenza A virus H19 subtype does not bind the canonical receptor sialic acid•H19 utilizes MHC class II proteins from distinct species for host cell entry•Mutating the putative canonical RBS of H19 restores sialic acid dependency•Residues in the MHC class II α chain confer species-specific entry of H19 Karakus et al. uncover H19 influenza A virus genomes in Northern 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.