Institute of Clinical and Molecular Virology, National Reference Centre for Retroviruses, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Virology. 2012 Feb 20;423(2):152-64. doi: 10.1016/j.virol.2011.11.026. Epub 2011 Dec 29.
Chronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and functional experiments. After attachment to PDC, viruses were taken up in an energy-dependent manner. The virions were located in compartments positive for caveolin; early endosomal antigen 1; Rab GTPases 5, 7 and 9; lysosomal-associated membrane protein 1. PDC harbored more virus in endocytic vesicles than CD4+ T cells (p<0.05). Blocking CD4 inhibited the uptake of virions into cytosolic and endosomal compartments. Dynasore, an inhibitor of dynamin-dependent endocytosis, not the fusion inhibitor T-20, reduced the HIV-1 induced IFN-alpha production. Altogether, our morphological and functional data support the role of endocytosis for the entry and IFN-alpha induction of HIV-1 in PDC.
慢性免疫激活是由浆细胞样树突状细胞（PDC）产生的干扰素（IFN）-α触发的，在 HIV-1 发病机制中起着重要作用。由于 HIV-1 的进入似乎对 PDC 的激活很重要，我们使用免疫电子显微镜、细胞分级分离、共聚焦成像和功能实验直接对这些细胞中的病毒进入进行了表征。病毒与 PDC 附着后，以能量依赖的方式被摄取。病毒颗粒位于富含小窝蛋白、早期内体抗原 1、Rab GTPases 5、7 和 9、溶酶体相关膜蛋白 1 的隔室中。PDC 中内吞小泡中的病毒比 CD4+T 细胞多（p<0.05）。阻断 CD4 抑制了病毒进入细胞质和内体隔室。动力蛋白依赖性内吞作用抑制剂 Dynasore 而不是融合抑制剂 T-20 降低了 HIV-1 诱导的 IFN-α产生。总之，我们的形态学和功能数据支持内吞作用在 HIV-1 进入和 IFN-α诱导 PDC 中的作用。
