HIV-1 infection of hematopoietic progenitor cells in vivo in humanized mice
HIV-1 infection of hematopoietic progenitor cells in vivo in humanized mice
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DOI：
10.1182/blood-2013-04-496950
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发表时间：
2013-09-26
期刊：
影响因子：
20.3
通讯作者：
Zack, Jerome A.
中科院分区：
文献类型：
--
作者：
Nixon, Christopher C.;Vatakis, Dimitrios N.;Zack, Jerome A.
从艾滋病毒/艾滋病流行的最初几天起，艾滋病毒感染就与造血缺陷有关。所有造血谱系的世代都面临感染。HIV损害正常血细胞发育的机制尚不清楚，中间造血祖细胞的直接感染尚未被确定为HIV相关造血病理学的来源。在这里，我们证明了在体外和体内感染的多个子集的高度纯化的中间造血祖细胞的野生型HIV。虽然直接感染明显具有细胞毒性，但我们发现一些受感染的祖细胞可以存活并携带前病毒DNA。我们报告中间造血祖细胞是一种新的感染靶点，其感染概率随着发育而增加。此外，非肥胖型糖尿病严重联合免疫缺陷常见g链敲除-骨髓肝-胸腺人源化小鼠提供了一个独特的模型，用于研究HIV感染对基于骨髓的人类造血的影响。
HIV infection has been associated with defective hematopoiesis since the earliest days of the HIV/AIDS epidemic. Generation of all hematopoietic lineages suffers in the face of infection. The mechanisms by which HIV impairs normal blood cell development remain unclear, and direct infection of intermediate hematopoietic progenitors has not been established as a source of HIV-associated hematopoietic pathology. Here, we demonstrate infection of multiple subsets of highly purified intermediate hematopoietic progenitors by wild-type HIV both in vitro and in vivo. Although direct infection is clearly cytotoxic, we find that some infected progenitors can survive and harbor proviral DNA. We report intermediate hematopoietic progenitors to be a novel target of infection and their permissivity to infection increases with development. Further, the nonobese diabetic severe combined immunodeficiency common g chain knockout-bone marrowliver-thymus humanized mouse provides a unique model for studying the impact of HIV infection on bone marrow-based human hematopoiesis.