Mucin 6 in seminal plasma binds DC-SIGN and potently blocks dendritic cell mediated transfer of HIV-1 to CD4+ T-lymphocytes

被引:46
作者
Stax, Martijn J. [1 ]
van Montfort, Thijs [1 ]
Sprenger, Richard R. [2 ]
Melchers, Mark [1 ]
Sanders, Rogier W. [1 ]
van Leeuwen, Elisabeth [3 ]
Repping, Sjoerd [3 ]
Pollakis, Georgios [1 ]
Speijer, Dave [2 ]
Paxton, William A. [1 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, Dept Med Microbiol,Lab Expt Virol, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Ctr Reprod Med, NL-1105 AZ Amsterdam, Netherlands
关键词
Mucin; 6; MUC6; DC-SIGN; HIV-1; Dendritic cells; HUMAN-IMMUNODEFICIENCY-VIRUS; SALT-STIMULATED LIPASE; HETEROSEXUAL TRANSMISSION; INHIBITION ASSAY; RISK-FACTORS; IN-VITRO; INFECTION; MILK; EXPRESSION; TYPE-1;
D O I
10.1016/j.virol.2009.06.011
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 SIDS-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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:203 / 211
页数:9
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