Department of Microbiology and Molecular Genetics and Department of Medicine (Division of Infectious Diseases), School of Medicine, University of California, Irvine, CA, USA.
Retrovirology. 2020 Apr 6;17(1):7. doi: 10.1186/s12977-020-00516-2.
Significant advances in the treatment of HIV infection have been made in the last three decades. Antiretroviral therapy (ART) is now potent enough to prevent virus replication and stop disease progression. However, ART alone does not cure the infection, primarily because HIV can persist in stable long-term reservoir cells including latently-infected CD4 + T cells. A central goal of the HIV research field is to devise strategies to eliminate these reservoirs and thereby develop a cure for HIV. This requires robust in vivo model systems to facilitate both the further characterization of persistent HIV reservoirs and evaluation of methods for eliminating latent virus. Humanized mice have proven to be versatile experimental models for studying many basic aspects of HIV biology. These models consist of immunodeficient mice transplanted with human cells or tissues, which allows development of a human immune system that supports robust infection with HIV. There are many potential applications for new generations of humanized mouse models in investigating HIV reservoirs and latency, but these models also involve caveats that are important to consider in experimental design and interpretation. This review briefly discusses some of the key strengths and limitations of humanized mouse models in HIV persistence studies.
在过去的三十年中,HIV 感染的治疗取得了重大进展。抗逆转录病毒疗法(ART)现在已经足够有效,可以防止病毒复制并阻止疾病进展。然而,单独的 ART 并不能治愈感染,主要是因为 HIV 可以在包括潜伏感染的 CD4+T 细胞在内的稳定的长期储存细胞中持续存在。HIV 研究领域的一个核心目标是设计策略来消除这些储存库,从而开发出 HIV 的治愈方法。这需要强大的体内模型系统来促进对持久性 HIV 储存库的进一步表征以及评估消除潜伏病毒的方法。人源化小鼠已被证明是研究 HIV 生物学许多基本方面的多功能实验模型。这些模型由移植了人类细胞或组织的免疫缺陷小鼠组成,这使得能够发展出支持 HIV 强大感染的人类免疫系统。新一代人源化小鼠模型在研究 HIV 储存库和潜伏期方面具有许多潜在的应用,但这些模型也存在一些注意事项,在实验设计和解释中需要考虑。本文简要讨论了人源化小鼠模型在 HIV 持续感染研究中的一些关键优势和局限性。