Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States.
The Skaggs Graduate Program in Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, United States.
Front Immunol. 2021 Apr 1;12:636775. doi: 10.3389/fimmu.2021.636775. eCollection 2021.
With the discovery of antiretroviral therapy, HIV-1 infection has transitioned into a manageable but chronic illness, which requires lifelong treatment. Nevertheless, complete eradication of the virus has still eluded us. This is partly due to the virus's ability to remain in a dormant state in tissue reservoirs, 'hidden' from the host's immune system. Also, the high mutation rate of HIV-1 results in escape mutations in response to many therapeutics. Regardless, the development of novel cures for HIV-1 continues to move forward with a range of approaches from immunotherapy to gene editing. However, to evaluate pathogenesis and the efficacy and safety of therapeutic approaches, a suitable animal model is necessary. To this end, the humanized mouse was developed by McCune in 1988 and has continued to be improved on over the past 30 years. Here, we review the variety of humanized mouse models that have been utilized through the years and describe their specific contribution in translating HIV-1 cure strategies to the clinic.
随着抗逆转录病毒疗法的发现，HIV-1 感染已转变为一种可控制但慢性的疾病，需要终身治疗。然而，我们仍然未能彻底清除病毒。这部分是由于病毒能够在组织储库中处于休眠状态，从而“躲避”宿主的免疫系统。此外，HIV-1 的高突变率导致其对许多治疗药物产生逃逸突变。尽管如此，针对 HIV-1 的新型治疗方法的开发仍在继续，包括从免疫疗法到基因编辑的多种方法。然而，为了评估发病机制以及治疗方法的疗效和安全性，需要一种合适的动物模型。为此，McCune 于 1988 年开发了人源化小鼠，并在过去 30 年中不断改进。在这里，我们回顾了多年来使用的各种人源化小鼠模型，并描述了它们在将 HIV-1 治愈策略转化为临床应用方面的具体贡献。
