title: A recombinant trimeric surfactant protein D carbohydrate recognition domain inhibits respiratory syncytial virus infection in vitro and in vivo.
abstract: The pulmonary collectin, lung surfactant protein D (SP-D), plays a role in host defense mediated by the interaction of surface carbohydrates of inhaled pathogens with the lectin domains of SP-D. Respiratory syncytial virus (RSV), the most important viral pathogen of neonates and infants, encodes a highly glycosylated attachment protein, G. Binding studies were performed with G protein from RSV (human, A2 strain) and both native and recombinant human SP-D. The effect of recombinant trimeric SP-D lectin domains (rSP-D) on the interaction between RSV and host cells was determined by two methods: an infectivity study with monolayers of Hep-2C cells and in vivo infections in BALB/c mice. These studies show that full-length and recombinant SP-D bind to RSV G protein in a concentration-dependent manner. Both EDTA and mannan inhibited binding of full-length SP-D. These results indicate that binding occurs via the carbohydrate recognition domain of the SP-D. The recombinant SP-D inhibited RSV infectivity in cell culture in a dose-dependent manner, giving 100% inhibition of replication. Intranasal administration of recombinant SP-D to RSV-infected mice inhibited replication of the virus in the lungs, reducing levels of lung virus by 80%. These results suggest that SP-D plays a major role in clearing RSV from the lungs.
authors.affiliation: GlaxoWellcome Medicines Research Centre, Stevenage, GB. tph94318@glaxowellcome.co.uk
authors.forename: T P
authors.initials: TP
authors.lastname: Hickling
authors.forename: H
authors.initials: H
authors.lastname: Bright
authors.forename: K
authors.initials: K
authors.lastname: Wing
authors.forename: D
authors.initials: D
authors.lastname: Gower
authors.forename: S L
authors.initials: SL
authors.lastname: Martin
authors.forename: R B
authors.initials: RB
authors.lastname: Sim
authors.forename: R
authors.initials: R
authors.lastname: Malhotra
mesh_terms: D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D015707:HN Protein; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D006023:Glycoproteins; D015707:HN Protein; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G