Mucin 6 in seminal plasma binds DC-SIGN and potently blocks dendritic cell mediated transfer of HIV-1 to CD4(+) T-lymphocytes.
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.
Stax
Martijn J
MJ
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.
van Montfort
Thijs
T
Sprenger
Richard R
RR
Melchers
Mark
M
Sanders
Rogier W
RW
van Leeuwen
Elisabeth
E
Repping
Sjoerd
S
Pollakis
Georgios
G
Speijer
Dave
D
Paxton
William A
WA
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
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