Humanized mouse models for preclinical evaluation of HIV cure strategies.
Humanized mouse models for preclinical evaluation of HIV cure strategies.
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DOI：
10.24875/aidsrev.22000013
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发表时间：
2022-10-25
期刊：
影响因子：
2.2
通讯作者：
Heredia, Alonso
中科院分区：
文献类型：
--
作者：
Fraker, Sally;Atkinson, Benjamin;Heredia, Alonso
尽管目前全世界都在关注COVID-19大流行，但艾滋病毒/艾滋病仍然是对公共卫生的重大威胁。迄今为止，艾滋病毒/艾滋病流行病已夺去了3 600多万人的生命，目前有近3 800万人患有这种疾病。尽管抗逆转录病毒疗法（ART）在控制艾滋病毒方面取得了不可否认的成功，但这些药物并不能治愈。在初次感染后不久，HIV以原病毒的形式整合到基因组中，主要是在CD4+ T细胞和组织巨噬细胞中。当不活跃转录时，原病毒对免疫系统和抗逆转录病毒疗法是隐藏的，被称为潜伏库。停止抗逆转录病毒治疗后，艾滋病毒可能从具有复制能力的原病毒中出现，并恢复健康细胞的感染。因此，这些潜伏的储存库是治愈艾滋病毒的主要障碍，清除它们仍然是一个优先事项。在治疗性疗法的发展中，一个至关重要的方面是在动物模型中证明疗效，例如人源化小鼠模型。因此，优化、标准化和验证人源化小鼠模型是当务之急。这篇综述文章的目的是提供现有人源化小鼠模型的最新进展，强调每种模型与HIV治愈研究相关的优点和缺点，并回顾正在研究的治疗方法。
Although the world is currently focused on the COVID-19 pandemic, HIV/AIDS remains a significant threat to public health. To date, the HIV/AIDS pandemic has claimed the lives of over 36 million people, while nearly 38 million people are currently living with the disease. Despite the undeniable success of antiretroviral therapy (ART) in controlling HIV, the medications are not curative. Soon after initial infection, HIV integrates into the genome as a provirus, primarily, within CD4+ T cells and tissue macrophages. When not actively transcribed, the provirus is hidden to the immune system and ART, and is referred to as a latent reservoir. Following ART discontinuation, HIV may emerge from the replication-competent proviruses and resumes the infection of healthy cells. Thus, these latent reservoirs are a major obstacle to an HIV cure, and their removal remains a priority. A vital aspect in the development of curative therapies is the demonstration of efficacy in an animal model, such as the humanized mouse model. Therefore, optimization, standardization, and validation of the humanized mouse model is a priority. The purpose of this review article is to provide an update on existing humanized mouse models, highlighting the advantages and disadvantages of each as they pertain to HIV cure studies, and to review the approaches to curative therapies that are under investigation.