Department of Medicine, McMaster University, Hamilton, ON, Canada.
McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
Front Immunol. 2021 Mar 5;11:617516. doi: 10.3389/fimmu.2020.617516. eCollection 2020.
Although antiretroviral therapy has transformed human immunodeficiency virus-type 1 (HIV-1) from a deadly infection into a chronic disease, it does not clear the viral reservoir, leaving HIV-1 as an uncurable infection. Currently, 1.2 million new HIV-1 infections occur globally each year, with little decrease over many years. Therefore, additional research is required to advance the current state of HIV management, find potential therapeutic strategies, and further understand the mechanisms of HIV pathogenesis and prevention strategies. Non-human primates (NHP) have been used extensively in HIV research and have provided critical advances within the field, but there are several issues that limit their use. Humanized mouse (Hu-mouse) models, or immunodeficient mice engrafted with human immune cells and/or tissues, provide a cost-effective and practical approach to create models for HIV research. Hu-mice closely parallel multiple aspects of human HIV infection and disease progression. Here, we highlight how innovations in Hu-mouse models have advanced HIV-1 research in the past decade. We discuss the effect of different background strains of mice, of modifications on the reconstitution of the immune cells, and the pros and cons of different human cells and/or tissue engraftment methods, on the ability to examine HIV-1 infection and immune response. Finally, we consider the newest advances in the Hu-mouse models and their potential to advance research in emerging areas of mucosal infections, understand the role of microbiota and the complex issues in HIV-TB co-infection. These innovations in Hu-mouse models hold the potential to significantly enhance mechanistic research to develop novel strategies for HIV prevention and therapeutics.
虽然抗逆转录病毒疗法已经将人类免疫缺陷病毒 1 型（HIV-1）从一种致命感染转变为慢性疾病，但它并不能清除病毒库，使 HIV-1成为一种无法治愈的感染。目前，全球每年有 120 万人新感染 HIV-1，多年来几乎没有减少。因此，需要进一步研究以推进当前的 HIV 管理状态，寻找潜在的治疗策略，并进一步了解 HIV 发病机制和预防策略的机制。非人类灵长类动物（NHP）在 HIV 研究中得到了广泛应用，并为该领域提供了重要进展，但存在一些限制其使用的问题。人源化小鼠（Hu-mouse）模型，或用人免疫细胞和/或组织移植的免疫缺陷小鼠，提供了一种具有成本效益和实用的方法来创建 HIV 研究模型。Hu-mice 与人 HIV 感染和疾病进展的多个方面密切相关。在这里，我们强调了过去十年中 Hu-mouse 模型的创新如何推动了 HIV-1 研究。我们讨论了不同背景品系的小鼠、对免疫细胞重建的修饰以及不同人类细胞和/或组织移植方法的优缺点，对检查 HIV-1 感染和免疫反应的能力的影响。最后，我们考虑了 Hu-mouse 模型的最新进展及其在粘膜感染等新兴领域研究中的潜在应用，以了解微生物群的作用和 HIV-TB 合并感染的复杂问题。这些 Hu-mouse 模型的创新有可能显著增强机制研究，从而开发出预防和治疗 HIV 的新策略。
