title: Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication.
abstract: The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate-binding activity and was dependent on glycosylation of gp120. Native dodecameric SP-D bound to HIV gp120 more strongly than native trimeric SP-D. Since one common polymorphic form of SP-D is predominantly expressed as trimers and associated with lower blood levels, these individuals may have less effective innate defence against HIV. A chimeric protein containing the N-terminal and collagen domains of SP-D linked to the neck and carbohydrate-recognition domains of MBL (called SP-D/MBL(neck+CRD)) had greater ability to bind to gp120 and inhibit virus replication than either SP-D or MBL. The enhanced binding of SP-D/MBL(neck+CRD) was dependent on assembly into higher molecular mass multimers (i.e. a trimeric form of the chimera did not bind to a greater extent than MBL). Hence, the enhanced binding of SP-D compared with MBL results from distinctive properties of its N-terminal and/or collagen domains. SP-D is present in lung and airway fluids, as well as in blood and various mucosal locations, and could, like MBL, play a role in restricting HIV transmission or replication in vivo.
authors.affiliation: Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Meschi
authors.affiliation: Department of Pathology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.affiliation: Center for HIV/AIDS Care and Research, Boston University Medical Center, Boston, MA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Skolnik
authors.affiliation: Center for HIV/AIDS Care and Research, Boston University Medical Center, Boston, MA, USA.
authors.forename: Khabirah
authors.initials: K
authors.lastname: Yahya
authors.affiliation: Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.affiliation: Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Leth-Larsen
authors.affiliation: Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Tornoe
authors.affiliation: Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Tesfaldet
authors.initials: T
authors.lastname: Tecle
authors.affiliation: Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.affiliation: Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D015699:HIV Envelope Protein gp120; D037663:Pulmonary Surfactant-Associated Protein D; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins