title: Mucin 6 in seminal plasma binds DC-SIGN and potently blocks dendritic cell mediated transfer of HIV-1 to CD4(+) T-lymphocytes.
abstract: Many viruses transmitted via the genital or oral mucosa have the potential to interact with dendritic cell-specific intercellular adhesion molecule-3 grabbing non integrin (DC-SIGN) expressed on immature dendritic cells (iDCs) that lie below the mucosal surface. These cells have been postulated to capture and disseminate human immunodeficiency virus type-1 (HIV-1) to CD4(+) lymphocytes, potentially through breaches in the mucosal lining. We have previously described that BSSL (bile salt-stimulated lipase) in human milk can bind DC-SIGN and block transfer. Here we demonstrate that seminal plasma has similar DC-SIGN blocking properties as BSSL in human milk. Using comparative SDS-PAGE and Western blotting combined with mass spectrometry we identified mucin 6 as the DC-SIGN binding component in seminal plasma. Additionally, we demonstrate that purified mucin 6 binds DC-SIGN and successfully inhibits viral transfer. Mucin 6 in seminal plasma may therefore interfere with the sexual transmission of HIV-1 and other DC-SIGN co-opting viruses.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Stax
authors.forename: Thijs
authors.initials: T
authors.lastname: van Montfort
authors.forename: Richard R
authors.initials: RR
authors.lastname: Sprenger
authors.forename: Mark
authors.initials: M
authors.lastname: Melchers
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.forename: Elisabeth
authors.initials: E
authors.lastname: van Leeuwen
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
authors.forename: Dave
authors.initials: D
authors.lastname: Speijer
authors.forename: William A
authors.initials: WA
authors.lastname: Paxton
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D055272:Mucin-6 / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D012661:Semen / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D055272:Mucin-6; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C524734:MUC6 protein, human