Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication.
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.
Meschi
Joseph
J
Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
Crouch
Erika C
EC
Department of Pathology, Washington University School of Medicine, St Louis, MO, USA.
Skolnik
Paul
P
Center for HIV/AIDS Care and Research, Boston University Medical Center, Boston, MA, USA.
Yahya
Khabirah
K
Center for HIV/AIDS Care and Research, Boston University Medical Center, Boston, MA, USA.
Holmskov
Uffe
U
Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark.
Leth-Larsen
Rikke
R
Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark.
Tornoe
Ida
I
Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark.
Tecle
Tesfaldet
T
Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
White
Mitchell R
MR
Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
Hartshorn
Kevan L
KL
Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA.
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*
D015699:HIV Envelope Protein gp120; D037663:Pulmonary Surfactant-Associated Protein D; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins