Modular Approaches to Understand the Immunobiology of Human Immunodeficiency Virus Latency.
Modular Approaches to Understand the Immunobiology of Human Immunodeficiency Virus Latency.
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了解人类免疫缺陷病毒潜伏期免疫生物学的模块化方法。
DOI：
10.1089/vim.2020.0171
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发表时间：
2021
期刊：
影响因子：
2.2
通讯作者：
Singh,NevilJ
中科院分区：
文献类型：
--
作者：
Wolf,Gideon;Singh,NevilJ
尽管在减缓获得性免疫缺陷综合征（艾滋病）的进展方面取得了进展，但对人类免疫缺陷病毒（艾滋病毒）没有可行的治愈方法。治愈的挑战主要是形成和维持一个潜伏的细胞库，这些细胞在复制能力和复制缺陷两种状态下窝藏病毒。这种静止细胞的小生态位已被鉴定为主要存在于静止和记忆性CD4+T细胞中，但是可以可靠地区分感染的T细胞与未感染的T细胞的参数（如果有的话）尚不清楚。此外，潜伏T细胞的迁移特性和特定解剖学储库难以在人体中以高分辨率测量。艾滋病毒的功能性治愈需要使用创新的新临床策略针对这一人群。这种方法的经验发展的一个限制是缺乏一个本土的艾滋病小动物模型。由于HIV不能有效地感染鼠细胞，因此探索涉及潜伏感染的T细胞归巢到深部组织部位、与基质相互作用并通过不同治疗方案持续存在的分子遗传学问题是具有挑战性的。本文的目的是讨论如何检查小鼠模型中T细胞的动力学可以为有效研究这些问题提供一个框架，即使没有用HIV感染小鼠。作为临床测量的结果，在早期人类HIV感染中发现的炎症和细胞因子环境正被越来越多地理解。重建这种环境的小鼠研究可能用于随后绘制在这种情况下激活的T细胞的命运以及它们的迁移路线。从本质上讲，这样的框架可以允许在小鼠中进行补充研究，以增强我们对HIV潜伏期生物学方面的理解。这可以是小动物HIV建模的模块化方法的基础，适用于临床前治疗策略的开发。
Despite advances in slowing the progression of acquired immunodeficiency syndrome (AIDS), there is no viable cure for human immunodeficiency virus (HIV). The challenge toward a cure is mainly the formation and maintenance of a latent reservoir of cells that harbor the virus in both replication-competent and replication-defective states. This small niche of quiescent cells has been identified to reside primarily in quiescent and memory CD4+T cells, but parameters that could reliably distinguish an infected T cell from an uninfected one, if any, are not clear. In addition, the migratory properties and specific anatomical reservoirs of latent T cells are difficult to measure at a high resolution in humans. A functional cure of HIV would require targeting this population using innovative new clinical strategies. One constraint toward the empirical development of such approaches is the absence of a native small animal model for AIDS. Since HIV does not efficiently infect murine cells, probing molecular-genetic questions involving latently infected T cells homing to deep tissue sites, interacting with stroma and persisting through different treatment regimens, is challenging. The goal of this article is to discuss how examining the dynamics of T cells in mouse models can provide a framework for effectively studying these questions, even without infecting mice with HIV. The inflammatory and cytokine milieu found in early human HIV infections are being increasingly understood as a result of clinical measurements. Mouse studies that recreate this milieu can potentially be used to subsequently map the fate of T cells activated in this context as well as their migratory routes. In essence, such a framework could allow complementary studies in mice to enhance our understanding of aspects of the biology of HIV latency. This can be the basis of a modular approach to small animal HIV modeling, amenable to preclinical curative strategy development.