Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment.
Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry. Here, we present the crystal structures of ISAV hemagglutinin-esterase unbound and complexed with receptor. Several distinctive features observed in ISAV HE are not seen in any other viral glycoprotein. The structures reveal a unique mode of receptor binding that is dependent on the oligomeric assembly of hemagglutinin-esterase. Importantly, ISAV hemagglutinin-esterase receptor engagement does not initiate conformational rearrangements, suggesting a distinct viral entry mechanism. This work improves our understanding of ISAV pathogenesis and expands our knowledge on the overall diversity of viral glycoprotein-mediated entry mechanisms. Finally, it provides an atomic-resolution model of the primary neutralizing antigen critical for vaccine development.
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Jonathan D
JD
Cook
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Azmiri
A
Sultana
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada jeff.lee@utoronto.ca.
Jeffrey E
JE
Lee
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D046829:Isavirus / Q000472:pathogenicity*; D011487:Protein Conformation; D000072417:Protein Domains; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D053838:Scattering, Small Angle; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment; D014961:X-Ray Diffraction
D006389:Hemagglutinins, Viral; D011991:Receptors, Virus; D014760:Viral Fusion Proteins; C060814:hemagglutinin esterase
hemagglutinin; infectious salmon anemia virus; orthomyxovirus; viral attachment; viral fusion