title: A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission.
abstract: The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show that only a modest change in the 1918 influenza hemagglutinin receptor binding site alters the transmissibility of this pandemic virus. Two amino acid mutations that cause a switch in receptor binding preference from the human alpha-2,6 to the avian alpha-2,3 sialic acid resulted in a virus incapable of respiratory droplet transmission between ferrets but that maintained its lethality and replication efficiency in the upper respiratory tract. Furthermore, poor transmission of a 1918 virus with dual alpha-2,6 and alpha-2,3 specificity suggests that a predominant human alpha-2,6 sialic acid binding preference is essential for optimal transmission of this pandemic virus. These findings confirm an essential role of hemagglutinin receptor specificity for the transmission of influenza viruses among mammals.
authors.affiliation: Influenza Branch, Mailstop G-16, Division of Viral and Ricksettial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA. tft9@cdc.gov
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Tumpey
authors.forename: Taronna R
authors.initials: TR
authors.lastname: Maines
authors.forename: Neal
authors.initials: N
authors.lastname: Van Hoeven
authors.forename: Laurel
authors.initials: L
authors.lastname: Glaser
authors.forename: Alicia
authors.initials: A
authors.lastname: Solórzano
authors.forename: Claudia
authors.initials: C
authors.lastname: Pappas
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: David E
authors.initials: DE
authors.lastname: Swayne
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D005289:Ferrets; D005690:Galactose / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D007251:Influenza, Human / Q000473:pathology / Q000635:transmission* / Q000821:virology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D009154:Mutation; D009666:Nose / Q000821:virology; D011991:Receptors, Virus / Q000378:metabolism; D012137:Respiratory System / Q000821:virology; D012794:Sialic Acids / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D006001:Glycoconjugates; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D012794:Sialic Acids; D005690:Galactose