title: Innate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D.
abstract: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study was to characterize antiviral interactions between SP-D and HNPs. Recombinant and/or natural forms of SP-D and related collectins and HNPs were tested for antiviral activity against two different strains of IAV. HNPs 1 and 2 did not inhibit viral hemagglutination activity, but they interfered with the hemagglutination-inhibiting activity of SP-D. HNPs had significant viral neutralizing activity against divergent IAV strains. However, the HNPs generally had competitive effects when combined with SP-D in assays using an SP-D-sensitive IAV strain. In contrast, cooperative antiviral effects were noted in some instances when relatively SP-D-resistant strains were treated with SP-D and HNPs. HNPs were found to bind to the neck and/or carbohydrate recognition domain of SP-D. This binding was specific because no, or minimal, binding to other collectins was found. HNPs precipitated SP-D from bronchoalveolar lavage fluid and reduced the antiviral activity of bronchoalveolar lavage fluid. HNP-1 and -2 differed somewhat in their independent antiviral activity and their binding to SP-D. These results are relevant to the early phase of host defense against IAV, and suggest a complex interplay between SP-D and HNPs at sites of active inflammation.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. khartsho@bu.edu
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Tesfaldet
authors.initials: T
authors.lastname: Tecle
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D023082:Defensins / Q000378:metabolism* / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D007113:Immunity, Innate; D047468:Immunoprecipitation; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D011485:Protein Binding / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D023082:Defensins; D004338:Drug Combinations; D037601:Mannose-Binding Lectin; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins