Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA.
Nat Med. 2010 Apr;16(4):446-51. doi: 10.1038/nm.2109. Epub 2010 Mar 7.
HIV causes a chronic infection characterized by depletion of CD4(+) T lymphocytes and the development of opportunistic infections. Despite drugs that inhibit viral spread, HIV infection has been difficult to cure because of uncharacterized reservoirs of infected cells that are resistant to highly active antiretroviral therapy (HAART) and the immune response. Here we used CD34(+) cells from infected people as well as in vitro studies of wild-type HIV to show 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 unique 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 major implications for understanding HIV bone marrow pathology and the mechanisms by which HIV causes persistent infection.
HIV 会引起慢性感染，其特征是 CD4(+) T 淋巴细胞耗竭和机会性感染的发展。尽管有抑制病毒传播的药物，但由于高度活跃的抗逆转录病毒疗法 (HAART) 和免疫反应无法作用的受感染细胞的未知储库，HIV 感染仍难以治愈。在这里，我们使用受感染人的 CD34(+) 细胞以及对野生型 HIV 的体外研究表明，CD34(+)多能造血祖细胞 (HPC) 会被感染和杀死。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。一种独特的报告 HIV 可以直接检测体外潜伏感染的细胞，证实了存在活跃和潜伏感染 HPC 的不同群体。这些发现对理解 HIV 骨髓病理学以及 HIV 引起持续性感染的机制具有重要意义。
