title: Interactions of alpha-, beta-, and theta-defensins with influenza A virus and surfactant protein D.
abstract: We have reported that the alpha-defensins human neutrophil peptides (HNP)-1 and HNP-2 neutralize and aggregate influenza A virus (IAV) and promote uptake of IAV by neutrophils. These alpha-defensins were also shown to bind to surfactant protein (SP)-D and reduce its antiviral activity. In this study, we examined retrocyclin (RC)1 and RC2, humanized versions of the antiviral theta-defensins found in the leukocytes of certain nonhuman primates. RC1 was just as effective as HNP-1-3 in neutralizing IAV, and RC2 and RC101 (an analog of RC1) were more effective. In contrast, human beta-defensins (HBDs) showed less neutralizing activity. Human defensins 5 and 6 (mainly produced by intestinal Paneth cells) had viral neutralizing activity similar to HNP-1-3. Like HNP-1-3, RCs induced viral aggregation and promoted the uptake of IAV by neutrophils. We used surface plasmon resonance to evaluate binding of defensins to SP-D. HBDs, HD6, and HNP-4 bound minimally to SP-D. HNP-1-3 and RCs bound SP-D with high affinity; however, unlike HNP-1 and HNP-2, RCs did not inhibit SP-D antiviral activity. HBDs also did not inhibit antiviral activity of SP-D. Given their strong neutralizing activity and compatibility with SP-D, RCs may provide attractive prototypes for designing therapeutics that can prevent or treat respiratory infections caused by IAV.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Doss
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Tesfaldet
authors.initials: T
authors.lastname: Tecle
authors.forename: Donald
authors.initials: D
authors.lastname: Gantz
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Grace
authors.initials: G
authors.lastname: Jung
authors.forename: Piotr
authors.initials: P
authors.lastname: Ruchala
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lehrer
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D006224:Cricetinae; D023082:Defensins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology* / Q000378:metabolism; D023084:alpha-Defensins / Q000276:immunology* / Q000378:metabolism; D023083:beta-Defensins / Q000276:immunology* / Q000378:metabolism
chemical_list: D023082:Defensins; D037663:Pulmonary Surfactant-Associated Protein D; D023084:alpha-Defensins; D023083:beta-Defensins; C450142:theta-defensin