尿激酶型纤溶酶原激活剂(uPA)系统由蛋白酶uPA组成,其受体(PLAUR/UPAR)。在生理条件下,uPA和PLAUR主要由血细胞表达,包括中性粒细胞,单核细胞,和巨噬细胞,并在细胞活化中发挥重要作用,附着力,迁移,和外渗。这里,我们报告说PLAUR,在巨噬细胞和树突状细胞(DC)中高度表达,但在CD4+T细胞中几乎不表达,抑制HIV-1子代病毒粒子从细胞膜的释放。沉默PLAUR显着增强了HIV-1在巨噬细胞和DC中的传播。我们进一步证明PLAUR位于细胞膜上以阻断HIV-1病毒体的释放。有趣的是,我们发现uPA损害了PLAUR介导的抑制作用,从而略微增强了原代巨噬细胞和DCs中HIV-1的产生.在没有PLAUR的情况下,这种由uPA诱导的增强作用被取消。总之,PLAUR是一种在巨噬细胞和DC中产生的新的抗HIV-1蛋白,它抑制HIV-1传播。这一发现可能为对抗HIV提供新的治疗靶标。
The urokinase-type plasminogen activator (
uPA) system consists of the proteinase
uPA, its receptor (PLAUR/uPAR). Under physiological conditions,
uPA and PLAUR are predominantly expressed by blood cells, including neutrophils, monocytes, and macrophages, and play important roles in cell activation, adhesion, migration, and extravasation. Here, we report that PLAUR, which is highly expressed in macrophages and dendritic cells (DCs) but hardly expressed in CD4+ T cells, inhibits the release of HIV-1 progeny virions from the cell membrane. Silencing PLAUR markedly enhanced the transmission of HIV-1 in macrophages and DCs. We further demonstrated that PLAUR is localized at the cell membrane to block the release of HIV-1 virions. Interestingly, we found that
uPA compromises the PLAUR-mediated inhibition to slightly enhance HIV-1 production in primary macrophages and DCs. In the absence of PLAUR, this enhanced effect induced by
uPA is abrogated. In conclusion, PLAUR is a new anti-HIV-1 protein produced in both macrophages and DCs where it inhibits HIV-1 transmission. This discovery may provide a novel therapeutic target for combating HIV.