The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice

The Establishment of an In Vivo HIV-1 Infection Model in Humanized B-NSG Mice
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人源化 B-NSG 小鼠体内 HIV-1 感染模型的建立

DOI:
10.1007/s12250-019-00181-6
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发表时间:
2019-12
期刊:
影响因子:
5.5
通讯作者:
Wang Jian-Hua
Wang Jian-Hua
中科院分区:
医学2区
文献类型:
--
作者:
Fan Tian-Jiao;Sun Li;Yang Xian-Guang;Jin Xia;Sun Wei-Wei;Wang Jian-Hua

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适合人类免疫缺陷病毒 1 型 (HIV-1) 感染的动物模型对于阐明病毒发病机制和评估体内抗病毒策略非常重要。在本研究中,检查了具有严重免疫缺陷表型的 B-NSG (NOD-PrkdcscidIl2rgtm1/Bcge) 小鼠,以确定此类模型的适用性。通过小鼠尾静脉注射将人外周血单核细胞 (PBMC) 移植到 B-NSG 小鼠体内,移植后 3 周即可在小鼠外周血和多种组织中观察到重新增殖的人 T 淋巴细胞。人源化小鼠可能被HIV-1感染,并且感染重现了在HIV-1感染者中观察到的T淋巴细胞动态特征,同时联合抗逆转录病毒疗法(cART)的施用抑制了病毒复制并恢复了T淋巴细胞异常。 HIV-1感染的人源化B-NSG小鼠的建立不仅提供了研究病毒和T细胞相互作用的模型,而且还可以成为评估抗病毒策略的有用工具。
Suitable animal models for human immunodeficiency virus type 1 (HIV-1) infection are important for elucidating viral pathogenesis and evaluating antiviral strategies in vivo. The B-NSG (NOD-PrkdcscidIl2rgtm1/Bcge) mice that have severe immune defect phenotype are examined for the suitability of such a model in this study. Human peripheral blood mononuclear cells (PBMCs) were engrafted into B-NSG mice via mouse tail vein injection, and the repopulated human T-lymphocytes were observed at as early as 3-weeks post-transplantation in mouse peripheral blood and several tissues. The humanized mice could be infected by HIV-1, and the infection recapitulated features of T-lymphocyte dynamic observed in HIV-1 infected humans, meanwhile the administration of combination antiretroviral therapy (cART) suppressed viral replication and restored T lymphocyte abnormalities. The establishment of HIV-1 infected humanized B-NSG mice not only provides a model to study virus and T cell interplays, but also can be a useful tool to evaluate antiviral strategies.
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