HIV-1 cellular and tissue replication patterns in infected humanized mice.
HIV-1 cellular and tissue replication patterns in infected humanized mice.
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DOI：
10.1038/srep23513
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发表时间：
2016-03-21
影响因子：
4.6
通讯作者：
Gendelman HE
中科院分区：
文献类型：
--
作者：
Araínga M;Su H;Poluektova LY;Gorantla S;Gendelman HE
人源化小鼠已经成为HIV-1病理生物学的测试平台，它反映了自然的人类疾病过程。它们用于研究艾滋病毒-1生物学、病毒学、免疫学、发病机制和治疗发展，已成为更成熟的艾滋病毒/艾滋病动物模型的有力替代。反映这种人类病理生物学的一个关键部分在于确定HIV-1感染的组织和细胞位置。为此，我们检测了CD34+造血干细胞移植病毒感染的NOD.Cg-Prkdcsord Il2rgtm1Wjl/SzJ小鼠的骨髓、血液、脾、肝、肠道、脑、肾和肺中病毒感染的组织部位。用流式细胞仪分析细胞，并从CD34+系阴性祖细胞、CD14+CD16+单核巨噬细胞以及中央、干细胞和效应记忆T细胞中分离出细胞。细胞分布和病毒生命周期依赖于组织间隔和感染时间。细胞亚群含有HIV-1的总DNA和整合DNA，以及不同比例的多剪接和非剪接RNA。这些数据支持这样的观点，即人源化的小鼠可以提供一种手段来检查HIV-1复制的多个部位，包括但不限于祖细胞和单核巨噬细胞，以前只有猕猴和人类才能做到这一点。
Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human.