title: Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D.
abstract: BACKGROUND
  Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr/Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D.
  
  
  METHODS
  Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro.
  
  
  RESULTS
  In initial experiments mAbs directed against different areas on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D.
  
  
  CONCLUSIONS
  These studies indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP-D can be useful for dissecting out different functional properties of the protein.
authors.affiliation: Boston University School of Medicine, Department of Medicine, Boston, MA, 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: Ida
authors.initials: I
authors.lastname: Tornoe
authors.forename: Grith L
authors.initials: GL
authors.lastname: Sorensen
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
mesh_terms: D001665:Binding Sites; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D006384:Hemagglutination / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000187:drug effects* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000503:physiopathology; D009500:Neutralization Tests; D011110:Polymorphism, Genetic; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D018406:Virus Physiological Phenomena
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D