title: Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice.
abstract: Following circulation of avian influenza H5 and H7 viruses in poultry, the hemagglutinin (HA) can acquire additional glycosylation sites, and the neuraminidase (NA) stalk becomes shorter. We investigated whether these features play a role in the pathogenesis of infection in mammalian hosts. From 1996 to 2007, H5N1 viruses with a short NA stalk have become widespread in several avian species. Compared to viruses with a long-stalk NA, viruses with a short-stalk NA showed a decreased capacity to elute from red blood cells and an increased virulence in mice, but not in chickens. The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans.
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: David E
authors.initials: DE
authors.lastname: Swayne
authors.forename: Colleen
authors.initials: C
authors.lastname: Thomas
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Rameix-Welti
authors.forename: Nadia
authors.initials: N
authors.lastname: Naffakh
authors.forename: Christine
authors.initials: C
authors.lastname: Warnes
authors.forename: Melanie
authors.initials: M
authors.lastname: Altholtz
authors.forename: Ruben
authors.initials: R
authors.lastname: Donis
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000818:Animals; D002645:Chickens; D004912:Erythrocytes / Q000378:metabolism; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism*; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice / Q000821:virology*; D009154:Mutation / Q000235:genetics; D009439:Neuraminidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009976:Orthomyxoviridae Infections; D013997:Time Factors; D014774:Virulence
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009439:Neuraminidase