Stax Martijn J, van Montfort Thijs, Sprenger Richard R, Melchers Mark, Sanders Rogier W, van Leeuwen Elisabeth, Repping Sjoerd, Pollakis Georgios, Speijer Dave, Paxton William A
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.
Virology. 2009 Sep 1;391(2):203-11. doi: 10.1016/j.virol.2009.06.011.
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.
许多通过生殖器或口腔黏膜传播的病毒有可能与未成熟树突状细胞（iDCs）表面表达的树突状细胞特异性细胞间黏附分子3结合非整合素（DC-SIGN）相互作用，这些未成熟树突状细胞位于黏膜表面下方。据推测，这些细胞可能通过黏膜内衬的破损处捕获并将1型人类免疫缺陷病毒（HIV-1）传播给CD4(+)淋巴细胞。我们之前曾描述过，人乳中的胆汁盐刺激脂肪酶（BSSL）可以结合DC-SIGN并阻断其转移。在此，我们证明精浆具有与人乳中BSSL类似的DC-SIGN阻断特性。通过比较SDS-PAGE和蛋白质印迹结合质谱分析，我们确定黏蛋白6是精浆中与DC-SIGN结合的成分。此外，我们证明纯化的黏蛋白6能结合DC-SIGN并成功抑制病毒转移。因此，精浆中的黏蛋白6可能会干扰HIV-1及其他利用DC-SIGN的病毒的性传播。
