The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response
The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response
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DOI：
10.1016/j.febslet.2011.10.018
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发表时间：
2011-11-16
期刊：
影响因子：
3.5
通讯作者：
Sadowski, Ivan
中科院分区：
文献类型：
--
作者：
Bernhard, Wendy;Barreto, Kris;Sadowski, Ivan
潜伏的人类免疫缺陷病毒1型（HIV - 1）原病毒不受当前艾滋病（获得性免疫缺陷综合征）疗法的影响。我们在此表明，毛壳菌素，一种SUV39H1组蛋白甲基转移酶抑制剂，可使潜伏的HIV - 1表达诱导增加25倍，同时产生极小的毒性且不引起T细胞活化。这种诱导与长末端重复序列（LTR）启动子处组蛋白H3赖氨酸9（H3K9）三甲基化的缺失以及H3K9乙酰化的相应增加有关。毛壳菌素与组蛋白去乙酰化酶（HDAC）抑制剂联合使用时，其作用会协同增强。这些结果表明，毛壳菌素可能提供一种清除潜伏HIV - 1细胞的疗法，或许可与其他染色质重塑药物联合使用。版权归英国皇家所有（C）2011，由爱思唯尔出版社代表欧洲生物化学会联合会出版。保留所有权利。
Latent HIV-1 (human immunodeficiency virus-1) provirus is unaffected by current AIDS (acquired immunodeficiency syndrome) therapies. We show here that chaetocin, an SUV39H1 histone methyltransferase inhibitor, causes 25-fold induction of latent HIV-1 expression, while producing minimal toxicity and without causing T cell activation. Induction is associated with loss of histone H3 lysine 9 (H3K9) trimethylation at the long terminal repeat (LTR) promoter, and a corresponding increase in H3K9 acetylation. The effect of chaetocin is amplified synergistically in combination with histone deacetylase (HDAC) inhibitors. These results indicate that chaetocin may provide a therapy to purge cells of latent HIV-1, possibly in combination with other chromatin remodeling drugs. Crown Copyright (C) 2011 Published by Elsevier B.V. on behalf of Federation of European Biochemical society. All rights reserved.