title: Interactions of influenza A virus with sialic acids present on porcine surfactant protein D.
abstract: Pigs can be infected with both human and avian influenza A virus (IAV) strains and are therefore considered to be important intermediates in the emergence of new IAV strains due to mixing of viral genes derived from human, avian, or porcine influenza viruses. These reassortant strains may have potential to cause pandemic influenza outbreaks in humans. The innate immune response against IAV plays a significant role in containment of IAV in the airways. We studied the interactions of IAV with porcine surfactant protein D (pSP-D), an important component of this first line defense system. Hemagglutination inhibition analysis shows that the distinct interactions of pSP-D with IAV mediated by the N-linked carbohydrate moiety in the carbohydrate recognition domain of pSP-D depend on the terminal sialic acids (SAs) present on this carbohydrate. Analysis by both lectin staining and by cleavage with linkage-specific sialidases shows that the carbohydrate of pSP-D is exclusively sialylated with alpha(2,6)-linked SAs, in contrast to surfactant protein A, which contains both alpha(2,3)- and alpha(2,6)-linked SAs on its N-linked carbohydrate. Enzymatic modification of the SA-linkages present on pSP-D demonstrates that the type of SA-linkage is important for its hemagglutination-inhibitory activity, and correlates with receptor-binding specificity of the IAV strains. The SAs present on pSP-D appear especially important for interactions with poorly glycosylated IAV strains. It remains to be elucidated to what extent the unique sialylation profile of pSP-D is involved in host range control of IAV in pigs, and whether it facilitates adaptation of avian or human IAV strains that can contribute to the production of reassortant strains in pigs.
authors.affiliation: Department of Biochemistry and Cell Biology, Graduate School of Animal Health, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.176, 3508 TD Utrecht, The Netherlands. m.vaneijk@vet.uu.nl
authors.forename: Martin
authors.initials: M
authors.lastname: van Eijk
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Batenburg
authors.forename: Arie B
authors.initials: AB
authors.lastname: Vaandrager
authors.forename: Lambert M G
authors.initials: LM
authors.lastname: van Golde
authors.forename: Henk P
authors.initials: HP
authors.lastname: Haagsman
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002645:Chickens; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009439:Neuraminidase / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000737:chemistry / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry; D011956:Receptors, Cell Surface; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011956:Receptors, Cell Surface; D012794:Sialic Acids; D009439:Neuraminidase