Boehm Daniela, Ott Melanie
1 Gladstone Institute of Virology and Immunology , San Francisco, California.
2 Department of Medicine, University of California , San Francisco, California.
AIDS Res Hum Retroviruses. 2017 Nov;33(S1):S8-S22. doi: 10.1089/aid.2017.0180.
A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection. We further explain the biology of PMTs and their effects on lysine and arginine methylation of histone and nonhistone proteins. We end with a focus on protein demethylases, their unique modes of action and their emerging influence on HIV infection. An outlook on the use of methylation-modifying agents in investigational HIV cure strategies is provided.
成功的艾滋病治愈策略可能需要逆转HIV潜伏状态以清除隐藏的病毒储存库，或者增强HIV潜伏状态以使HIV转录永久沉默。表观遗传修饰剂在体外和离体实验中显示出作为抗潜伏疗法的潜力，但也会影响病毒生命周期的其他步骤。在这篇综述中，我们总结了我们对参与HIV感染的细胞DNA和蛋白质甲基转移酶（PMT）以及去甲基酶的了解。我们描述了DNA甲基转移酶的生物学特性和功能，以及它们在HIV感染中存在争议的作用。我们进一步解释了PMT的生物学特性及其对组蛋白和非组蛋白赖氨酸和精氨酸甲基化的影响。最后，我们重点介绍蛋白质去甲基酶、它们独特的作用方式以及它们对HIV感染日益显著的影响。本文还对甲基化修饰剂在艾滋病治愈研究策略中的应用前景进行了展望。
