Molecular Virology and Gene Therapy, KU Leuven, Leuven, Flanders, Belgium.
Curr Opin HIV AIDS. 2024 May 1;19(3):95-101. doi: 10.1097/COH.0000000000000844. Epub 2024 Feb 27.
Currently, HIV-infected patients are treated with antiretroviral therapy. However, when the treatment is interrupted, viral rebound occurs from latently infected cells. Therefore, scientists aim to develop an HIV-1 cure which eradicates or permanently silences the latent reservoir.
Previously, scientists focused on the shock-and-kill cure strategy, which aims to eradicate the latent reservoir using latency-reactivating agents. Limited success shifts the interest towards the block-and-lock cure approach, which aims to achieve a functional cure by "blocking" HIV-1 transcription and "locking" the provirus in a deep latent state, resistant to treatment-interruption. In this strategy, latency promoting agents are used to induce transcriptional silencing and alter the epigenetics environment at the HIV promotor.
For the block-and-lock cure strategy to succeed more investigation into the transcriptional and epigenetic regulation of HIV-1 gene expression is necessary to design optimal latency-promoting agents. In this review, we will discuss the latency promoting agents that have been described in literature during the past 2 years (2022-2023).
目前，HIV 感染者接受抗逆转录病毒治疗。然而，当治疗中断时，潜伏感染的细胞会发生病毒反弹。因此，科学家们旨在开发一种 HIV-1 治愈方法，以根除或永久沉默潜伏库。
以前，科学家们专注于“震撼-杀伤”治愈策略，该策略旨在使用潜伏激活剂来根除潜伏库。有限的成功促使人们转向“阻断-锁定”治愈方法，该方法旨在通过“阻断”HIV-1 转录并将前病毒锁定在深度潜伏状态来实现功能性治愈，从而抵抗治疗中断。在该策略中，使用潜伏促进剂诱导转录沉默并改变 HIV 启动子的表观遗传学环境。
为了使“阻断-锁定”治愈策略取得成功，需要对 HIV-1 基因表达的转录和表观遗传学调控进行更多的研究，以设计最佳的潜伏促进剂。在这篇综述中，我们将讨论在过去 2 年（2022-2023 年）文献中描述的潜伏促进剂。
