Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Mucosal Immunol. 2013 Mar;6(2):427-34. doi: 10.1038/mi.2012.87. Epub 2012 Sep 19.
Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean-squared displacement was calculated. The mobility of beads increased significantly in CVM compared with CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function.
宫颈和阴道上皮组织是男性向女性传播过程中预防 HIV Ⅰ型(HIV-1)感染的主要屏障。宫颈黏液(CM)由宫颈内产生,并以宫颈阴道黏液(CVM)的形式在局部和阴道腔中形成一层。为了研究在 HIV-1 传播过程中每种黏液类型的潜在屏障功能,我们使用荧光显微镜在体外地量化了 CM 和 CVM 中 HIV-1 的迁移能力。通过数字跟踪病毒粒子和 200nm 的聚乙二醇化珠,并计算均方根位移。与 CM 相比,珠粒在 CVM 中的迁移明显增加,这与 CVM 中已知的粘蛋白浓度降低一致。出乎意料的是,在珠粒扩散不受阻碍的相同 CVM 样本中,HIV-1 的扩散受到明显阻碍。病毒运输的抑制与包膜无关。我们的结果揭示了 CVM 中一种以前未知的活性,它能够阻碍 HIV-1 的迁移,从而增强黏膜屏障功能。