HIV潜伏是当前实现根治的主要难点。HIV潜伏和致病机制研究、治疗手段的开发缺乏合适的动物模型。当前人源化小鼠模型虽然在上述领域中开展应用，但仍存在不足之处如不能系统地重构人免疫系统等。B-NSG是目前公认的免疫缺陷程度最高、最适合人源细胞或组织移植的商业化工具小鼠。人造血干细胞移植该小鼠，可成功重建人免疫系统，在感染和免疫等领域有较广泛的应用。前期曾移植人外周血PBMC至该小鼠，成功构建人源化。在此基础上，本课题拟利用B-NSG小鼠，移植人脐带血CD34+细胞, 构建人源化小鼠; 随后感染HIV病毒株，并利用抗逆转录病毒一线药抑制HIV复制，建立新型人源化B-NSG/HIV潜伏感染模型;并初步利用该模型评价前期在细胞水平筛选的HIV潜伏激活剂。该模型的建立不但可用于评价根治策略，还可为研究HIV潜伏和致病机制提供有效的工具。

HIV latency is a main obstacle for eradication. The study of HIV latency, viral pathogenesis and the development of cure strategies lack a suitable animal model. Although the current humanized mice model has been applied in the above-mentioned fields, there are still shortcomings such as the inability to reconstruct the human immune system. B-NSG is commercial mice, has the severest immunodeficiency, and is currently recognized as the most suitable for transplantation of human cells or tissues. The transplantation of human stem cells to the mice can successfully reconstruct a variety of cells of the human immune system, which has been widely used in the fields of infection and immunity. In our preliminary data, we have transplanted human PBMCs to the mice for successful humanization. So based on these experiences, this project intends to use the B-NSG mice, transplanted with human umbilical cord blood CD34+ cells to construct humanized mice; after challenge with HIV, viral acute infection will be blocked with injection of antiretroviral first-line drugs, and a novel B-NSG/HIV latent infection model is acquired; the mice model is further used to preliminarily evaluate the HIV latency reverse agents that have been identified in this laboratory by using cell-based systems. The humanized B-NSG/HIV latency mice model can be used not only to evaluate HIV cure strategies, but also to provide an effective tool for the mechanistic study of HIV latency and pathogenesis.