title: 1918 Influenza receptor binding domain variants bind and replicate in primary human airway cells regardless of receptor specificity.
abstract: The 1918 influenza pandemic caused ~50 million deaths. Many questions remain regarding the origin, pathogenicity, and mechanisms of human adaptation of this virus. Avian-adapted influenza A viruses preferentially bind α2,3-linked sialic acids (Sia) while human-adapted viruses preferentially bind α2,6-linked Sia. A change in Sia preference from α2,3 to α2,6 is thought to be a requirement for human adaptation of avian influenza viruses. Autopsy data from 1918 cases, however, suggest that factors other than Sia preference played a role in viral binding and entry to human airway cells. Here, we evaluated binding and entry of five 1918 influenza receptor binding domain variants in a primary human airway cell model along with control avian and human influenza viruses. We observed that all five variants bound and entered cells efficiently and that Sia preference did not predict entry of influenza A virus to primary human airway cells evaluated in this model.
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States; Diagnostic Medicine and Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States.
authors.forename: A Sally
authors.initials: AS
authors.lastname: Davis
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States; Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Chertow
authors.affiliation: Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Schwartzman
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States; Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
authors.forename: Jon
authors.initials: J
authors.lastname: Suzich
authors.affiliation: Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
authors.forename: Sara
authors.initials: S
authors.lastname: Alsaaty
authors.affiliation: Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
authors.forename: Carolea
authors.initials: C
authors.lastname: Logun
authors.affiliation: Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States.
authors.forename: James H
authors.initials: JH
authors.lastname: Shelhamer
authors.affiliation: Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. Electronic address: taubenbergerj@niaid.nih.gov.
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D001665:Binding Sites; D001980:Bronchi / Q000166:cytology; D004847:Epithelial Cells / Q000821:virology*; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D064149:Influenza Pandemic, 1918-1919; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011991:Receptors, Virus / Q000378:metabolism*; D014132:Trachea / Q000166:cytology; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid
keywords: Hemagglutinin; Influenza A virus; Pandemic; Receptor binding