Nguyen Deborah Greene, Hildreth James E K
Department of Pharmacology, Johns Hopkins School of Medicine, Baltimore, USA.
Eur J Immunol. 2003 Feb;33(2):483-93. doi: 10.1002/immu.200310024.
The human immunodeficiency virus (HIV) is an enveloped virus whose surface glycoprotein gp120 binds CD4 on target cell membranes to initiate infection. About half of the carbohydrates on gp120 are terminally mannosylated, a pattern common to many pathogens. We have examined the ability of macrophage mannose receptor (MMR) on primary monocyte-derived macrophages to bind HIV and facilitate its transmission to T cells. We adapted the tyramide signal amplification system for fluorescence detection of HIV bound to macrophages. Our data show that approximately 60% of the initial association of HIV with macrophages that lack expression of DC-SIGN (a dendritic cell-specific ICAM-3 receptor/HIV-1-binding protein) is MMR mediated, as evidenced by inhibition with mannan, D-mannose, EDTA, and soluble mannose-binding lectin, but not by D-galactose. This inhibition is not seen in cells that lack MMR. Macrophages are able to mediate transmission of bound HIV to co-cultured T cells, and this transmission is blocked up to 80% by inhibitors of MMR binding. Unlike virus bound to DC-SIGN, macrophage-bound HIV has a slightly lower half-life compared to free virus, with no transmission in co-culture observed beyond 24 h after virus binding to macrophages. Results obtained with endocytosis inhibitors indicate that this decrease in viral longevity is due to rapid internalization of macrophage-bound HIV. Together, these results suggest a substantial role for MMR in the binding and transmission of HIV-1 by macrophages.
人类免疫缺陷病毒（HIV）是一种包膜病毒，其表面糖蛋白gp120与靶细胞膜上的CD4结合以引发感染。gp120上约一半的碳水化合物末端被甘露糖基化，这是许多病原体共有的模式。我们研究了原代单核细胞衍生巨噬细胞上的巨噬细胞甘露糖受体（MMR）结合HIV并促进其向T细胞传播的能力。我们采用酪胺信号放大系统对结合到巨噬细胞上的HIV进行荧光检测。我们的数据表明，在缺乏DC-SIGN（一种树突状细胞特异性ICAM-3受体/HIV-1结合蛋白）表达的巨噬细胞中，HIV与巨噬细胞的初始结合约60%是由MMR介导的，甘露聚糖、D-甘露糖、EDTA和可溶性甘露糖结合凝集素可抑制这种结合，而D-半乳糖则不能。在缺乏MMR的细胞中未观察到这种抑制作用。巨噬细胞能够将结合的HIV介导至共培养的T细胞，并且MMR结合抑制剂可将这种传播阻断达80%。与结合到DC-SIGN的病毒不同，与巨噬细胞结合的HIV的半衰期比游离病毒略短，在病毒与巨噬细胞结合后24小时以上的共培养中未观察到传播。内吞作用抑制剂的结果表明，病毒寿命的这种缩短是由于与巨噬细胞结合的HIV快速内化所致。总之，这些结果表明MMR在巨噬细胞结合和传播HIV-1中起重要作用。
