title: Inhibition of DC-SIGN-mediated trans infection of T cells by mannose-binding lectin.
abstract: Some dendritic cells (DC) express a cell-surface lectin called 'dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin' (DC-SIGN). DC-SIGN has been shown to mediate a type of infection called 'trans' infection, where DC bind human immunodeficiency virus (HIV) and efficiently transfer the virus to T cells. We investigated the possibility that mannose-binding lectin (MBL), a soluble lectin that functions as a recognition molecule in innate immunity and that binds to HIV, could block trans infection mediated by DC-SIGN. Binding studies with glycoprotein (gp)120/gp41-positive and -negative virus preparations suggested that DC-SIGN and MBL bind primarily to glycans on gp120/gp41, as opposed to glycans on host-cell-derived proteins, indicating a close overlap in the binding site of the two lectins and supporting the notion that MBL could prevent binding of HIV to DC-SIGN. Preincubation of X4, R5 or dual-tropic HIV strains with MBL prevented DC-SIGN-mediated trans infection of T cells. The mechanism of MBL blocking trans infection of T cells was at least partly caused by blocking of virus binding to DC-SIGN positive cells. This study shows that MBL prevents DC-SIGN-mediated trans infection of T cells in vitro and suggests that in infected persons, MBL may inhibit DC-SIGN-mediated uptake and spread of HIV.
authors.affiliation: Department of Immunology/Microbiology, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA. gspear@rush.edu
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Spear
authors.forename: M Reza
authors.initials: MR
authors.lastname: Zariffard
authors.forename: Ji
authors.initials: J
authors.lastname: Xin
authors.forename: Mohammed
authors.initials: M
authors.lastname: Saifuddin
mesh_terms: D001667:Binding, Competitive; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006678:HIV / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D037601:Mannose-Binding Lectin; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin