Quentin M R Gibaut, Luisa P Mori, Susana T Valente
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引用次数: 0
摘要
综述的目的:本综述重点介绍了 HIV 转录和表观遗传潜伏机制方面的进展,并概述了目前消除或阻断 HIV-1 潜伏库的治疗方法:据报道,新的宿主因子可以调节 HIV-1 的转录和潜伏。染色质亲和纯化策略和质谱分析(ChAP-MS)发现,伴侣蛋白 p32 通过与病毒转录激活因子 Tat 相互作用,在 HIV-1 转录调控中发挥着重要作用。同样,通过 shRNA 筛选发现,甲基转移酶 SMYD5 也通过调节 Tat 的活性来促进 HIV-1 的转录激活。摘要: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,是治疗中断后病毒反弹的源头。要治愈艾滋病毒,就必须在没有抗逆转录病毒疗法(ART)的情况下消除潜伏库或阻断潜伏前病毒的再激活。了解调节艾滋病病毒转录和再激活的机制和关键角色可能会促进治疗的进步。在此,我们总结了有关宿主因子在 HIV 转录调控中作用的最新发现。
HIV-1 transcriptional modulation: novel host factors and prospective therapeutic strategies.
Purpose of review: 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.
Recent findings: 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.
Summary: 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.
期刊介绍:
Published bimonthly and offering a unique and wide ranging perspective on the key developments in the field, each issue of Current Opinion in HIV and AIDS features hand-picked review articles from our team of expert editors. With six disciplines published across the year – including HIV and ageing, a HIV vaccine, and epidemiology – every issue also contains annotated reference detailing the merits of the most important papers.