Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Drug Discov Today. 2013 Jun;18(11-12):541-51. doi: 10.1016/j.drudis.2012.12.008. Epub 2012 Dec 25.
The latent reservoir for HIV-1 in resting CD4(+) T cells remains a major barrier to HIV-1 eradication, even though highly active antiretroviral therapy (HAART) can successfully reduce plasma HIV-1 levels to below the detection limit of clinical assays and reverse disease progression. Proposed eradication strategies involve reactivation of this latent reservoir. Multiple mechanisms are believed to be involved in maintaining HIV-1 latency, mostly through suppression of transcription. These include cytoplasmic sequestration of host transcription factors and epigenetic modifications such as histone deacetylation, histone methylation and DNA methylation. Therefore, strategies targeting these mechanisms have been explored for reactivation of the latent reservoir. In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations.
HIV-1 潜伏在静止 CD4(+)T 细胞中的病毒库仍然是 HIV-1 根除的主要障碍，尽管高效抗逆转录病毒疗法（HAART）可以成功地将血浆 HIV-1 水平降低到临床检测方法的检测下限以下，并逆转疾病进展。拟议的根除策略涉及潜伏库的再激活。人们认为有多种机制参与维持 HIV-1 的潜伏期，主要通过抑制转录。这些机制包括将宿主转录因子隔离在细胞质中，以及组蛋白去乙酰化、组蛋白甲基化和 DNA 甲基化等表观遗传修饰。因此，已经探索了针对这些机制的策略，以激活潜伏库。在这篇综述中，我们讨论了目前针对根除的药理学方法，重点介绍了小分子潜伏逆转剂及其作用机制、优势和局限性。
