HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs.

HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs.
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DOI:
10.1038/nm.2109
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发表时间:
2010-04
期刊:
影响因子:
82.9
通讯作者:
--
中科院分区:
医学1区
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--
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HIV导致一种慢性感染,其特征是CD4+T淋巴细胞耗尽和发生机会性感染。尽管有抑制病毒传播的药物,但艾滋病毒一直很难治愈,因为感染细胞的特点不明,对高效的抗逆转录病毒治疗和免疫反应具有抵抗力。在这里,我们使用来自感染者的CD34+细胞以及野生型HIV的体外研究来证明CD34+多能造血祖细胞(HPC)的感染和杀伤。在一些HPC中,我们检测到潜伏感染,这种感染在细胞培养中稳定存在,直到分化因子激活病毒基因表达。一种在体外直接检测潜伏感染细胞的新型报告HIV证实了存在不同的活跃和潜伏感染的HPC群体。这些发现对于了解HIV骨髓病理和HIV导致持续感染的机制具有重要意义。
HIV causes a chronic infection characterized by depletion of CD4+ T lymphocytes and development of opportunistic infections. Despite drugs that inhibit viral spread, HIV has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy and the immune response. Here we used CD34+ cells from infected people as well as in vitro studies of wild type HIV to demonstrate infection and killing of CD34+ multipotent hematopoietic progenitor cells (HPCs). In some HPCs, we detected latent infection that stably persisted in cell culture until viral gene expression was activated by differentiation factors. A novel reporter HIV that directly detects latently infected cells in vitro confirmed the presence of distinct populations of active and latently infected HPCs. These findings have important implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.