title: Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D.
abstract: BACKGROUND
  Surfactant protein D (SP-D) plays an important role in innate defense against influenza A viruses (IAVs) and other pathogens.
  
  
  METHODS
  We tested antiviral activities of recombinant human SP-D against a panel of IAV strains that vary in glycosylation sites on their hemagglutinin (HA). For these experiments a recombinant version of human SP-D of the Met11, Ala160 genotype was used after it was characterized biochemically and structurally.
  
  
  RESULTS
  Oligosaccharides at amino acid 165 on the HA in the H3N2 subtype and 104 in the H1N1 subtype are absent in collectin-resistant strains developed in vitro and are important for mediating antiviral activity of SP-D; however, other glycans on the HA of these viral subtypes also are involved in inhibition by SP-D. H3N2 strains obtained shortly after introduction into the human population were largely resistant to SP-D, despite having the glycan at 165. H3N2 strains have become steadily more sensitive to SP-D over time in the human population, in association with addition of other glycans to the head region of the HA. In contrast, H1N1 strains were most sensitive in the 1970s-1980s and more recent strains have become less sensitive, despite retaining the glycan at 104. Two H5N1 strains were also resistant to inhibition by SP-D. By comparing sites of glycan attachment on sensitive vs. resistant strains, specific glycan sites on the head domain of the HA are implicated as important for inhibition by SP-D. Molecular modeling of the glycan attachment sites on HA and the carbohydrate recognition domain of SPD are consistent with these observations.
  
  
  CONCLUSIONS
  Inhibition by SP-D correlates with presence of several glycan attachment sites on the HA. Pandemic and avian strains appear to lack susceptibility to SP-D and this could be a contributory factor to their virulence.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston MA, USA. khartsho@bu.edu
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Richard
authors.initials: R
authors.lastname: Webby
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Tesfaldet
authors.initials: T
authors.lastname: Tecle
authors.forename: Clark
authors.initials: C
authors.lastname: Pan
authors.forename: Susan
authors.initials: S
authors.lastname: Boucher
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Moreland
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Scheule
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry; D006031:Glycosylation / Q000187:drug effects; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000502:physiology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000008:administration & dosage* / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D006389:Hemagglutinins, Viral; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins