Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo
Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo
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DOI：
10.1182/blood.v91.8.2672.2672_2672_2678
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发表时间：
1998-04-15
期刊：
影响因子：
20.3
通讯作者：
McCune, JM
中科院分区：
文献类型：
--
作者：
Jenkins, M;Hanley, MB;McCune, JM
人免疫缺陷病毒-1（human immunodeficiency virus-1，HIV-1）感染对多系造血祖细胞的影响尚不明确。该模型用于研究HIV-1感染对早期造血祖细胞功能的影响。我们发现，无论是谱系限制和多谱系造血祖细胞被耗尽的分子克隆或HIV-1的主要分离感染的移植物。造血祖细胞（包括CD 34（+）细胞、甲基纤维素中的集落形成单位和长期培养起始细胞）的耗竭发生在胸腺细胞耗竭开始前几天，表明随后胸腺细胞数量的快速下降至少部分是由于胸腺祖细胞的丢失。在早于胸腺内T祖细胞阶段的造血细胞中未检测到高频率的HIV-1前病毒基因组，尽管在感染的移植物中这些细胞被耗尽。在来自感染移植物的祖细胞的集落中也未检测到前病毒基因组。这些数据表明，HIV-1感染中断了体内谱系限制性和多谱系造血，并表明在没有直接病毒感染的情况下发生早期造血祖细胞的耗竭。(C)1998年，美国血液学会。
It is still uncertain whether multilineage hematopoietic progenitor cells are affected by human immunodeficiency virus-1 (HIV-1) infection in vivo, The SCID-hu Thy/Liv model is permissive of long-term multilineage human hematopoiesis, including T lymphopoiesis. This model was used to investigate the effects of HIV-1 infection on early hematopoietic progenitor function. We found that both lineage-restricted and multilineage hematopoietic progenitors were depleted from grafts infected with either a molecular clone or a primary isolate of HIV-1. Depletion of hematopoietic progenitors (including CD34(+) cells, colony-forming units in methylcellulose, and long-term culture-initiating cells) occurred several days before the onset of thymocyte depletion, indicating that the subsequent rapid decline in thymocyte numbers was due at least in part to loss of thymocyte progenitors. HIV-1 proviral genomes were not detected at high frequency in hematopoietic cells earlier than the intrathymic T-progenitor cell stage, despite the depletion of such cells in infected grafts. Proviral genomes were also not detected in colonies derived from progenitor cells from infected grafts. These data demonstrate that HIV-1 infection interrupts both lineage-restricted and multilineage hematopoiesis in vivo and suggest that depletion of early hematopoietic progenitor cells occurs in the absence of direct viral infection. (C) 1998 by The American Society of Hematology.