Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, Belgium.
Viral Pathogenesis Group, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy.
Methods Mol Biol. 2022;2407:3-15. doi: 10.1007/978-1-0716-1871-4_1.
The introduction of combination antiretroviral therapy (cART) has switched HIV-1 infection from a lethal disease to a chronic one. Indeed, cART is a lifelong treatment since its interruption is always followed by a rapid rebound of viremia from both cellular and anatomical viral reservoirs where the integrated HIV-1 provirus remains transcriptionally silent or maintains low-levels of viral replication, thereby preventing HIV-1 eradication. As therapeutic approach, the "shock and kill" strategy has emerged with the main objective to reactivate HIV-1 transcription from latency by using latency reversing agents (LRAs) prior to kill the reactivated infected cells by improving host immune responses. In this context, the development of tools such as HIV-1 latently infected cell lines have drastically increased our knowledge about HIV-1 latency and how to counteract this highly heterogeneous phenomenon. In this chapter, we will describe several chronically HIV-1 infected T-lymphocytic cell lines as useful surrogate models to study reversible HIV-1 proviral latency in CD4+ T cells in vitro before approaching more complex and expensive models.
联合抗逆转录病毒疗法（cART）的引入将 HIV-1 感染从致命疾病转变为慢性疾病。事实上，由于中断 cART 治疗后，病毒血症会迅速从细胞和解剖学病毒库中反弹，其中整合的 HIV-1 前病毒仍处于转录沉默或维持低水平病毒复制状态，从而阻止 HIV-1 被清除，因此 cART 需要终身治疗。作为一种治疗方法，“冲击和杀伤”策略已经出现，其主要目标是通过使用潜伏逆转剂（LRAs）来重新激活潜伏的 HIV-1 转录，然后通过提高宿主免疫反应来杀伤重新激活的感染细胞。在这种情况下，HIV-1 潜伏感染细胞系等工具的发展极大地增加了我们对 HIV-1 潜伏和如何对抗这种高度异质性现象的了解。在本章中，我们将描述几种慢性 HIV-1 感染的 T 淋巴细胞系，它们是体外研究 CD4+ T 细胞中可逆 HIV-1 前病毒潜伏的有用替代模型，然后再研究更复杂和昂贵的模型。
