Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology.
The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, Jupiter, Florida, USA.
Curr Opin HIV AIDS. 2023 Sep 1;18(5):264-272. doi: 10.1097/COH.0000000000000808. Epub 2023 Jul 17.
This review highlights advances in HIV transcription and epigenetic latency mechanisms and outlines current therapeutic approaches to eliminate or block the HIV-1 latent reservoir.
Novel host factors have been reported to modulate HIV-1 transcription and latency. Chromatin affinity purification strategies followed by mass spectrometry (ChAP-MS) identified the chaperone protein p32 to play an important role in HIV-1 transcriptional regulation via interactions with the viral transcriptional activator Tat. Similarly, an shRNA screen identified the methyltransferase SMYD5 contributing to HIV-1 transcriptional activation also by modulating Tat activity. These new factors, among others, represent potential druggable targets that could be explored in the 'block-and-lock' or 'shock-and-kill' approaches.
The HIV-1 latent reservoir is established early after infection, persists during antiretroviral therapy, and is the source of viral rebound after treatment interruption. An HIV cure requires either eliminating this reservoir or blocking latent proviral reactivation in the absence of antiretroviral therapy (ART). Understanding the mechanisms and key-players modulating HIV transcriptional and reactivation may facilitate therapeutic advancements. Here we summarize, the latest findings on host factors' roles in HIV transcriptional regulation.
目的综述：本综述强调了 HIV 转录和表观遗传潜伏期机制的进展，并概述了目前消除或阻断 HIV-1 潜伏库的治疗方法。
最新发现：已有报道称新型宿主因子可调节 HIV-1 的转录和潜伏期。染色质亲和纯化策略结合质谱（ChAP-MS）鉴定出伴侣蛋白 p32 通过与病毒转录激活物 Tat 相互作用，在 HIV-1 转录调控中发挥重要作用。同样，shRNA 筛选发现甲基转移酶 SMYD5 通过调节 Tat 活性也有助于 HIV-1 转录激活。这些新的因子，以及其他因子，代表了潜在的可成药靶点，可以在“阻断和锁定”或“冲击和杀伤”方法中进行探索。
总结：HIV-1 潜伏库在感染后早期建立，在抗逆转录病毒治疗期间持续存在，并且是治疗中断后病毒反弹的来源。HIV 治愈需要消除这个库，或者在没有抗逆转录病毒治疗（ART）的情况下阻止潜伏前病毒的重新激活。了解调节 HIV 转录和重新激活的机制和关键因素可能有助于治疗进展。在这里，我们总结了宿主因子在 HIV 转录调控中的作用的最新发现。
