title: Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model.
abstract: There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses.
authors.affiliation: Viral Zoonoses and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Otte
authors.affiliation: Public Health England, Porton Down, United Kingdom.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Marriott
authors.affiliation: Viral Zoonoses and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Dreier
authors.affiliation: Public Health England, Porton Down, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Dove
authors.affiliation: Department for Computational Biology of Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Kyra
authors.initials: K
authors.lastname: Mooren
authors.affiliation: Department for Computational Biology of Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Klingen
authors.affiliation: Department for Molecular Pathology, Institute of Pathology, University Hospital Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Public Health England, Porton Down, United Kingdom.
authors.forename: Katy-Anne
authors.initials: KA
authors.lastname: Thompson
authors.affiliation: Public Health England, Porton Down, United Kingdom.
authors.forename: Allan
authors.initials: A
authors.lastname: Bennett
authors.affiliation: Department for Molecular Pathology, Institute of Pathology, University Hospital Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.affiliation: Viral Zoonoses and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.|Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: van Riel
authors.affiliation: Department for Computational Biology of Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Alice C
authors.initials: AC
authors.lastname: McHardy
authors.affiliation: Public Health England, Porton Down, United Kingdom.
authors.forename: Miles W
authors.initials: MW
authors.lastname: Carroll
authors.affiliation: Viral Zoonoses and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.|Center for Structure and Cell Biology in Medicine, University of Lübeck, Germany.
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005289:Ferrets / Q000821:virology*; D016679:Genome, Viral / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics*; D061985:Madin Darby Canine Kidney Cells; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000821:virology*; D012137:Respiratory System / Q000821:virology; D012794:Sialic Acids / Q000378:metabolism; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012794:Sialic Acids