THE SCID-HU MOUSE AS A MODEL FOR HIV-1 INFECTION
THE SCID-HU MOUSE AS A MODEL FOR HIV-1 INFECTION
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DOI：
10.1038/363732a0
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发表时间：
1993-06-24
期刊：
影响因子：
64.8
通讯作者：
ZACK, JA
中科院分区：
文献类型：
--
作者：
ALDROVANDI, GM;FEUER, G;ZACK, JA
在正常的胎儿个体发育过程中，胸腺是最早发现CD4阳性细胞的器官之一。因此，这个器官可能是人类免疫缺陷病毒1型(HIV-1)在子宫内感染的最早目标之一。在感染HIV-1的成人和儿童中，以及在一些感染了HIV-1的妇女流产的胎儿中，已经看到了HIV-1感染的细胞和胸腺的病理异常。由于缺乏合适的动物模型系统，HIV-1致病机理的研究一直受到阻碍。在这里，我们以SCID-HU小鼠为模型，研究病毒感染对人体组织的影响。严重联合免疫缺陷(SCID)缺陷型7，8小鼠为纯合子。将人胎肝和胸腺植入小鼠肾被膜下构建模型。一个联合的人体器官发育，使人类胸腺细胞正常成熟。在将HIV-1直接接种到这些植入物中后，我们观察到在感染后的几周内人类携带CD4的细胞严重耗尽。这与植入物中病毒载量的增加有关。因此，SCID-Hu小鼠可能是研究HIV-1诱导的病理学的一个有用的体内系统。
DURING normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the thymus1. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women2-5. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse6 as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect7,8. The model is constructed by implanting human fetal fiver and thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology.