title: Contemporary avian influenza A virus subtype H1, H6, H7, H10, and H15 hemagglutinin genes encode a mammalian virulence factor similar to the 1918 pandemic virus H1 hemagglutinin.
abstract: Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backbone, differing only by hemagglutinin subtype expressed. Viruses expressing the avian H1, H6, H7, H10, and H15 subtypes were pathogenic in mice and cytopathic in normal human bronchial epithelial cells, in contrast to H2-, H3-, H5-, H9-, H11-, H13-, H14-, and H16-expressing viruses. Mouse pathogenicity was associated with pulmonary macrophage and neutrophil recruitment. These data suggest that avian influenza virus hemagglutinins H1, H6, H7, H10, and H15 contain inherent mammalian virulence factors and likely share a key virulence property of the 1918 virus. Consequently, zoonotic infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals.
  
  
  OBJECTIVE
  Influenza viruses from birds can cause outbreaks in humans and may contribute to the development of pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its main surface protein, an H1 subtype hemagglutinin, was identified as a key mammalian virulence factor. In a previous study, a 1918 virus expressing an avian H1 gene was as virulent in mice as the reconstructed 1918 virus. Here, a set of avian influenza viruses was constructed, differing only by hemagglutinin subtype. Viruses with the avian H1, H6, H7, H10, and H15 subtypes caused severe disease in mice and damaged human lung cells. Consequently, infections with avian influenza viruses bearing one of these hemagglutinins may cause enhanced disease in mammals, and therefore surveillance for human infections with these subtypes may be important in controlling future outbreaks.
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lindsey M
authors.initials: LM
authors.lastname: Pujanauski
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: A Sally
authors.initials: AS
authors.lastname: Davis
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Schwartzman
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Chertow
authors.affiliation: Institute for Systems Biology, Seattle, Washington, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baxter
authors.affiliation: Institute for Systems Biology, Seattle, Washington, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Scherler
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.affiliation: Department of Veterinary Preventive Medicine, Ohio State University, Columbus, Ohio, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Slemons
authors.affiliation: Institute for Systems Biology, Seattle, Washington, USA.
authors.forename: Kathie-Anne
authors.initials: KA
authors.lastname: Walters
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kash
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA taubenbergerj@niaid.nih.gov.
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D000818:Animals; D001717:Birds; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D005585:Influenza in Birds / Q000821:virology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008322:Mammals; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D016865:Reassortant Viruses / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D059386:Reverse Genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037521:Virulence Factors