Macrophage-derived HIV-1 carries bioactive TGF-beta
Macrophage-derived HIV-1 carries bioactive TGF-beta
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DOI：
10.1038/s41598-019-55615-8
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发表时间：
2019-12-13
影响因子：
4.6
通讯作者：
Margolis, Leonid
中科院分区：
文献类型：
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作者：
Arakelyan, Anush;Petersen, Jennifer D.;Margolis, Leonid
在感染者中，受感染的T细胞和巨噬细胞是产生HIV-1的主要细胞。HIV-1从感染细胞释放后，会结合各种细胞膜蛋白，其中一些是这些细胞所特有的。然而，细胞编码蛋白在病毒粒子中的功能在很大程度上仍不清楚。我们分别使用细胞特异性标记物CD36和CD27，用流式病毒测定法在HIV感染者的血浆中鉴定巨噬细胞和T细胞来源的HIV-1病毒粒子。我们用四种不同的方法证明了病毒粒子上的CD36通过一种配体凝血酶反应蛋白1(TSP-1)与免疫抑制细胞因子转化生长因子-β(TGF-β)结合。单个病毒粒子的流式病毒学分析显示，转化生长因子-β在CD36+病毒粒子上表达(平均28.2%+/-6.6%(n=3))，而在CD27+病毒粒子上不表达(平均1%+/-0.1%(n=3))。捕获的CD36+病毒粒子上存在的转化生长因子-β分子具有生物学活性，通过报告细胞系进行评估。将转化生长因子-β通过HIV病毒粒子运送到HIV靶细胞可能会影响它们，在病毒发病机制中发挥重要作用。
Infected T cells and macrophages are the main producers of HIV-1 in infected individuals. Upon release from infected cells, HIV-1 incorporates various cellular membrane proteins, some of which are specific for these cells. However, the functions of cell-encoded proteins in virions remain largely unknown. We performed flow virometry to identify, in plasma of HIV-infected individuals, macrophage- and T-cell-derived HIV-1 virions, using cell-specific markers CD36 and CD27, respectively. Using four different methods, we demonstrated that CD36 on virions binds the immunosuppressive cytokine transforming growth factor beta (TGF-beta) through a ligand, thrombospondin one (TSP-1). Flow virometry of individual virions showed that TGF-beta was present on CD36+ virions (average, 28.2% +/- 6.6% (n = 3)) but not on CD27+ virions (average, 1%+/- 0.1% (n = 3)). TGF-beta molecules present on captured CD36+ virions were biologically active, as evaluated with a reporter cell line. Delivery of TGF-beta on HIV virions to HIV target cells may affect them, playing a significant role in viral pathogenesis.