title: Lung surfactant protein A provides a route of entry for respiratory syncytial virus into host cells.
abstract: Lung surfactant protein A (SP-A) has a central role in host defense mediated by the interaction of surface carbohydrates of inhaled pathogens with the lectin domains of SP-A. 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 human SP-A. The effect of SP-A on the interaction between RSV and host cells was determined by two methods: an infectivity study with monolayers of Hep-2C cells and by interleukin-8 (IL-8) release from buffy coat (BC) cells. SP-A binds to RSV G-protein in a concentration-dependent manner that is inhibitable by both ethylenediamine tetraacetic acid (EDTA) and mannan, indicating that binding is through the carbohydrate recognition domain of the SP-A and a carbohydrate moiety of the G-protein. The level of RSV infection of Hep-2C cells increases with increasing concentrations of SP-A. The amount of IL-8 released by BC cells in the presence of RSV is increased with SP-A concentrations of 2.9 microg/mL or greater. Our results show that SP-A enhances the attachment of RSV and subsequent entry into host cells. The effect of SP-A on viral uptake by epithelial cells and macrophage may determine both innate and adaptive immune responses to RSV.
authors.affiliation: Cellular Biochemistry Unit, GlaxoWellcome, Medicines Research Centre, Stevenage, Hertfordshire, United Kingdom. tph94318@glaxowellcome.co.uk
authors.forename: T P
authors.initials: TP
authors.lastname: Hickling
authors.forename: R
authors.initials: R
authors.lastname: Malhotra
authors.forename: H
authors.initials: H
authors.lastname: Bright
authors.forename: W
authors.initials: W
authors.lastname: McDowell
authors.forename: E D
authors.initials: ED
authors.lastname: Blair
authors.forename: R B
authors.initials: RB
authors.lastname: Sim
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015707:HN Protein; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007962:Leukocytes; D008351:Mannans / Q000494:pharmacology; D011510:Proteolipids / Q000302:isolation & purification / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000302:isolation & purification / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism / Q000472:pathogenicity*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000378:metabolism*; D014774:Virulence
chemical_list: D015707:HN Protein; D016209:Interleukin-8; D008351:Mannans; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G