The development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.

中文翻译：

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超越捕鼠器：当前和新兴的人源化小鼠和大鼠模型，用于研究针对 HIV 感染和相关病理的预防和治疗策略

在过去的几十年中，针对人类免疫缺陷病毒 (HIV) 感染的安全有效的联合抗逆转录病毒疗法的开发已显着降低了 HIV 相关的发病率和死亡率。此外，抗逆转录病毒药物提供了一种有效的预防艾滋病毒传播的手段。尽管取得了这些进展，但仍存在重大限制。即无法消除 HIV 储存库、无法逆转淋巴组织损伤以及缺乏预防 HIV 传播的有效疫苗。评估用于消除 HIV 储存库和预防 HIV 传播的疗法和疫苗的安全性和有效性需要强大的体内模型。由于 HIV 是一种人类特异性病原体，它针对造血谱系细胞和淋巴组织，HIV-宿主相互作用的体内动物模型需要结合人类造血谱系细胞和淋巴组织。在这篇综述中，我们将讨论构建具有人类淋巴组织和/或造血谱系细胞的小鼠模型，称为人类免疫系统 (HIS) 人源化小鼠。这些 HIS 人源化小鼠模型可以支持功能性人类先天性和适应性免疫细胞以及初级（胸腺）和次级（脾）淋巴组织的发育。我们将讨论 HIS 人源化小鼠模型在评估针对 HIV 储存库和相关免疫病理学的治疗方法的安全性和有效性方面的应用，并描绘由候选 HIV 疫苗引发的人类免疫反应。