title: The molecular basis of the pathogenicity of the Dutch highly pathogenic human influenza A H7N7 viruses.
abstract: During the highly pathogenic avian influenza (HPAI) H7N7 virus outbreak in The Netherlands in 2003, 88 infected persons suffered from mild illnesses, and 1 died of pneumonia. Here, we studied which of the 14 amino acid substitutions observed between the fatal case (FC) virus and a conjunctivitis case (CC) virus determined the differences in virus pathogenicity. In virus-attachment experiments, the CC and FC viruses revealed marked differences in binding to the lower respiratory tract of humans. In a mouse model, the hemagglutinin (HA) gene of the FC virus was a determinant of virus tissue distribution. The lysine at position 627 of basic polymerase 2 (PB2) of the FC virus was the major determinant of pathogenicity and tissue distribution. Thus, remarkable similarities were revealed between recent HPAI H5N1 and H7N7 viruses. We conclude that the influenza virus HA and PB2 genes should be the prime targets for molecular surveillance during outbreaks of zoonotic HPAI viruses.
authors.affiliation: Department of Virology and National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Munster
authors.forename: Emmie
authors.initials: E
authors.lastname: de Wit
authors.forename: Debby
authors.initials: D
authors.lastname: van Riel
authors.forename: Walter E P
authors.initials: WE
authors.lastname: Beyer
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D003236:Conjunctivitis, Viral / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000235:genetics; D007251:Influenza, Human / Q000235:genetics / Q000473:pathology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D009426:Netherlands; D011200:Poultry; D016865:Reassortant Viruses / Q000235:genetics / Q000472:pathogenicity*; D053585:Virus Attachment
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus