title: The N-linked glycosylation site at position 158 on the head of hemagglutinin and the virulence of H5N1 avian influenza virus in mice.
abstract: N-linked glycosylation of the influenza virus hemagglutinin (HA) protein plays crucial roles in HA structure and function, evasion of neutralizing antibodies, and susceptibility to innate soluble antiviral factors. The N-linked glycosylation site at position 158 of highly pathogenic H5N1 virus was previously shown to affect viral receptor-binding preference. H5N1 viruses show heterogeneity with respect to the presence of this glycosylation site. Clade 1 viruses that caused outbreaks in Southeast Asia in 2004 contained this glycosylation site, while the site is absent in the more recent clade 2 viruses. Here, we show that elimination of this glycosylation site increases viral virulence in mice. The mutant lacking the glycosylation site at position 158 showed unaltered growth kinetics in vitro and a comparable level of sensitivity to a major antiviral protein found in respiratory secretions, surfactant protein D (SP-D).
authors.affiliation: Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Ornpreya
authors.initials: O
authors.lastname: Suptawiwat
authors.forename: Chompunuch
authors.initials: C
authors.lastname: Boonarkart
authors.forename: Warunya
authors.initials: W
authors.lastname: Chakritbudsabong
authors.forename: Mongkol
authors.initials: M
authors.lastname: Uiprasertkul
authors.forename: Pilaipan
authors.initials: P
authors.lastname: Puthavathana
authors.forename: Witthawat
authors.initials: W
authors.lastname: Wiriyarat
authors.forename: Prasert
authors.initials: P
authors.lastname: Auewarakul
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D057131:Immune Evasion / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000821:virology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D019562:Viral Load; D037521:Virulence Factors / Q000235:genetics; D014779:Virus Replication / Q000502:physiology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037663:Pulmonary Surfactant-Associated Protein D; D037521:Virulence Factors