Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses.
Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses.
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发表时间：
2007
期刊：
影响因子：
20.3
通讯作者：
Satoru Watanabe;K. Terashima;Shinrai Ohta;S. Horibata;Misako Yajima;Y. Shiozawa;M. Dewan;Zhong Yu;Mamoru Ito;T. Morio;N. Shimizu;M. Honda;N. Yamamoto
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作者：
Satoru Watanabe;K. Terashima;Shinrai Ohta;S. Horibata;Misako Yajima;Y. Shiozawa;M. Dewan;Zhong Yu;Mamoru Ito;T. Morio;N. Shimizu;M. Honda;N. Yamamoto
开发有效的艾滋病毒/艾滋病模型的关键是生产一种动物模型，该模型能复制HIV-1的长期活跃复制，然后引发病毒特异性免疫反应。在这项研究中，我们构建了人源化的非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）/白细胞介素-2受体γ链敲除（IL 2 R γ（null））（hNOG）小鼠移植人脐带血来源的造血干细胞，最终发展成为人类B细胞，T细胞，和其他单核细胞/巨噬细胞和4树突状细胞与淋巴组织中淋巴滤泡样结构的产生。CXCR 4和CCR 5抗原在外周血、脾脏和骨髓中的CD 4+细胞上被识别，而在胸腺CD 4 + T细胞上未检测到CCR 5。hNOG小鼠在感染CCR 5和CXCR 4嗜性HIV-1分离株超过40天后显示出显著的、持久的病毒血症，R5病毒感染的动物在脾脏和骨髓中显示出高水平的HIV-DNA拷贝，X4病毒感染的动物在胸腺和脾脏中显示出高水平的HIV-DNA拷贝。此外，我们在显示高病毒感染率的动物中检测到抗HIV-1 Env gp 120和Gag p24特异性抗体。因此，hNOG小鼠通过产生特异性抗体来反映人类系统性HIV感染，这表明它们可能具有作为HIV/AIDS动物模型用于研究HIV发病机制和免疫应答的潜力。
Critical to the development of an effective HIV/AIDS model is the production of an animal model that reproduces long-lasting active replication of HIV-1 followed by elicitation of virus-specific immune responses. In this study, we constructed humanized nonobese diabetic/severe combined immunodeficiency (NOD/SCID)/interleukin-2 receptor gamma-chain knockout (IL2Rgamma(null)) (hNOG) mice by transplanting human cord blood-derived hematopoietic stem cells that eventually developed into human B cells, T cells, and other monocytes/macrophages and 4 dendritic cells associated with the generation of lymphoid follicle-like structures in lymphoid tissues. Expressions of CXCR4 and CCR5 antigens were recognized on CD4+ cells in peripheral blood, the spleen, and bone marrow, while CCR5 was not detected on thymic CD4+ T cells. The hNOG mice showed marked, long-lasting viremia after infection with both CCR5- and CXCR4-tropic HIV-1 isolates for more than the 40 days examined, with R5 virus-infected animals showing high levels of HIV-DNA copies in the spleen and bone marrow, and X4 virus-infected animals showing high levels of HIV-DNA copies in the thymus and spleen. Furthermore, we detected both anti-HIV-1 Env gp120- and Gag p24-specific antibodies in animals showing a high rate of viral infection. Thus, the hNOG mice mirror human systemic HIV infection by developing specific antibodies, suggesting that they may have potential as an HIV/AIDS animal model for the study of HIV pathogenesis and immune responses.