Human Hematopoietic Stem Cell (HSC)-Engrafted NSG Mice for HIV Latency Research.
Human Hematopoietic Stem Cell (HSC)-Engrafted NSG Mice for HIV Latency Research.
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DOI：
10.1007/978-1-0716-1871-4_17
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发表时间：
2022
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联合抗逆转录病毒疗法 (cART) 可抑制大多数患者的 HIV，但无法治愈 HIV 感染。治愈的主要挑战是血液和组织中静息的 CD4+ T 细胞中存在潜在的具有复制能力的 HIV，这些细胞在去除 cART 后会重新引发感染。这种储存库的半衰期长是治愈的主要障碍，消除它是当前艾滋病毒研究的主要目标。重现艾滋病毒潜伏期的动物模型可以为艾滋病毒潜伏期的建立提供重要见解，更重要的是，可以测试艾滋病毒根除策略。我们描述了一种通过肝内注射人脐带血来源的 CD34+ 造血干细胞 (HSC) 到新生 NSG 小鼠（HSC-NSG 小鼠模型）中生成人源化小鼠的方案。我们还描述了在该模型中建立 HIV 潜伏期的协议。 HSC-NSG 小鼠为一种将 HIV 基因编辑和组织中 HIV 抑制相结合的方法提供了概念验证，该方法可能治愈感染人类的 HIV。
Combination antiretroviral therapy (cART) suppresses HIV in most patients, but it cannot cure HIV infection. The main challenge to a cure is the presence of latent replication-competent HIV in resting CD4+ T cells in blood and tissues, which reignite infection after cART removal. The long half-life of this reservoir is a major barrier to a cure, and its elimination is a main goal of current HIV research. Animal models that recapitulate HIV latency can provide key insights into the establishment of HIV latency and, more importantly, enable the testing of HIV eradication strategies. We describe a protocol for the generation of humanized mice by intrahepatic injection of human cord blood-derived CD34+ hematopoietic stem cells (HSC) into newborn NSG mice, the HSC-NSG mouse model. We also describe a protocol for establishing HIV latency in this model. HSC-NSG mice have provided proof-of-concept for an approach combining HIV gene editing and HIV suppression in tissues that may cure HIV in infected humans.