Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection
Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection
复制标题
DOI：
10.1128/cvi.00403-06
复制
发表时间：
2007-04-01
影响因子：
--
通讯作者：
Uittenbogaart, Christel H.
中科院分区：
文献类型：
--
作者：
An, Dong Sung;Poon, Betty;Uittenbogaart, Christel H.
本研究的目的是建立一个小动物模型，研究人类免疫缺陷病毒1型（HIV-1）在血液和初级和次级淋巴器官的发病机制。经腹腔注射人CD 34（+）细胞的Rag 2（-/-）γ（-/-）（c）小鼠产生功能性人免疫系统（HIS），在动物的胸腺、外周血、脾脏和骨髓中发现人造血细胞（下文中这些动物被称为HIS-Rag 2（-/-）γ（-/-）（c）小鼠）。HIS-Rag 2（-/-）gamma（-/-）（c）小鼠感染少量嗜CCR 5的HIV-1。检测了外周血和淋巴器官中人细胞的病毒复制和免疫表型变化。检测外周血、胸腺和脾组织以及骨髓中人细胞的生产性感染。感染动物中CD 4（+）T细胞与CD 8（+）T细胞的比例下降。尽管未检测到特异性抗HIV-1免疫应答，但在接种动物中发现了针对病毒制剂中存在的未鉴定胎牛血清蛋白的免疫球蛋白M（IgM）和IgG抗体。因此，我们已经证明HIS-Rag 2（-/-）gamma（-/-）（c）小鼠模型可用于感染低剂量的CCR 5嗜性HIV-1，其最常在原发感染期间传播。HIS-Rag 2（-/-）gamma（-/-）（c）小鼠可以作为研究HIV-1发病机制和测试潜在HIV-1疗法的小动物模型，使用该模型进行的研究可能取代一些使用非人灵长类动物进行的长期和昂贵的研究。
The goal of this study was to develop a small-animal model to study human immunodeficiency virus type 1 (HIV-1) pathogenesis in blood and primary and secondary lymphoid organs. Rag2(-/-)gamma(-/-)(c) mice that are neonatally injected with human CD34(+) cells develop a functional human immune system (HIS), with human hematopoietic cells being found in the thymuses, peripheral blood, spleens, and bone marrow of the animals (hereafter these animals are referred to as HIS-Rag2(-/-)gamma(-/-)(c) mice). HIS-Rag2(-/-)gamma(-/-)(c) mice were infected with small amounts of CCR5-tropic HIV-1. Viral replication and immunophenotypic changes in the human cells in peripheral blood and lymphoid organs were examined. The productive infection of human cells in peripheral blood, thymus and spleen tissue, and bone marrow was detected. Ratios of CD4(+) T cells to CD8(+) T cells in the infected animals declined. Although no specific anti-HIV-1 immune responses were detected, inummoglobulin M (IgM) and IgG antibodies to an unidentified fetal calf serum protein present in the virus reparation were found in the inoculated animals. Thus, we have shown that the HIS-Rag2(-/-)gamma(-/-)(c) mouse model can be used for infection with low doses of CCR5-tropic HIV-1, which is most commonly transmitted during primary infections. HIS-Rag2(-/-)gamma(-/-)(c) mice can serve as a small-animal model for investigating HIV-1 pathogenesis and testing potential HIV-1 therapies, and studies with this model may replace some long and costly studies with nonhuman primates.