Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Methods Mol Biol. 2022;2407:229-251. doi: 10.1007/978-1-0716-1871-4_17.
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.
联合抗逆转录病毒疗法（cART）可抑制大多数患者体内的 HIV，但无法治愈 HIV 感染。治愈的主要挑战是潜伏在血液和组织中静止 CD4+T 细胞中的具有复制能力的 HIV，cART 去除后会重新引发感染。该储存库的半衰期长是治愈的主要障碍，消除它是当前 HIV 研究的主要目标。可重现 HIV 潜伏期的动物模型可为 HIV 潜伏期的建立提供关键见解，更重要的是，使 HIV 清除策略的测试成为可能。我们描述了一种通过将人脐血来源的 CD34+造血干细胞（HSC）经肝内注射到新生 NSG 小鼠中生成人源化小鼠的方案，即 HSC-NSG 小鼠模型。我们还描述了在该模型中建立 HIV 潜伏期的方案。HSC-NSG 小鼠为一种联合 HIV 基因编辑和组织中 HIV 抑制的方法提供了概念验证，该方法可能治愈感染人类的 HIV。
