New latency-promoting agents for a block-and-lock functional cure strategy.

Current opinion in HIV and AIDS Pub Date : 2024-05-01 Epub Date: 2024-02-27 DOI:10.1097/COH.0000000000000844
Eline Pellaers, Alexe Denis, Zeger Debyser
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Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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).

用于阻断和锁定功能性治疗策略的新型延迟促进剂。
审查目的:目前,艾滋病病毒感染者接受抗逆转录病毒治疗。然而,当治疗中断时,潜伏感染细胞中的病毒会反弹。因此,科学家们的目标是开发一种能够根除或永久沉默潜伏库的 HIV-1 治疗方法:以前,科学家们的研究重点是 "冲击-杀灭 "治愈策略,该策略旨在使用潜伏激活剂根除潜伏库。这种方法旨在通过 "阻断 "HIV-1 的转录,并将病毒 "锁定 "在深度潜伏状态,从而达到功能性治愈的目的。在这一策略中,潜伏促进剂被用来诱导转录沉默和改变 HIV 启动子的表观遗传学环境:为使阻断-锁定治疗策略取得成功,有必要对 HIV-1 基因表达的转录和表观遗传调控进行更多研究,以设计出最佳的潜伏促进剂。在这篇综述中,我们将讨论过去两年(2022-2023 年)文献中描述的潜伏期促进剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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