Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA.
J Infect Dis. 2021 Feb 15;223(12 Suppl 2):46-53. doi: 10.1093/infdis/jiaa681.
Antiretroviral therapy effectively controls human immunodeficiency virus (HIV) infection. However, a reservoir of latently infected cells persists under suppressive therapy, constituting a major barrier to an HIV cure. The block-and-lock approach to a functional cure aims at the transcriptional and epigenetic silencing of proviruses, blocking viral reactivation in the absence of therapy, preventing disease progression and transmission, despite the presence of detectable integrated proviruses. This approach has been put forward for exploration based on the activity of didehydro-cortistatin A, an inhibitor of the HIV transcriptional activator Tat. Here we review the mechanisms by which didehydro-cortistatin A inhibition of Tat's feedback loop transcriptional amplification results in epigenetic silencing of the HIV promoter, and we discuss the benefits and limitations of the block-and-lock approach for an HIV cure.
抗逆转录病毒疗法可有效控制人类免疫缺陷病毒（HIV）感染。然而，在抑制性治疗下，潜伏感染细胞的储库仍然存在，这是 HIV 治愈的主要障碍。功能性治愈的“阻断-锁定”方法旨在使前病毒的转录和表观遗传沉默，在没有治疗的情况下阻断病毒的重新激活，防止疾病进展和传播，尽管存在可检测到的整合前病毒。基于 HIV 转录激活物 Tat 的抑制剂二氢皮质甾酮 A 的活性，提出了这种方法进行探索。在这里，我们回顾了二氢皮质甾酮 A 抑制 Tat 的反馈环转录放大作用导致 HIV 启动子表观遗传沉默的机制，并讨论了“阻断-锁定”方法用于 HIV 治愈的益处和局限性。
