The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response

被引：76
作者：
Bernhard, Wendy
Barreto, Kris
Saunders, Amy [2 ]
Dahabieh, Matthew S.
Johnson, Pauline [2 ]
Sadowski, Ivan [1 ]
机构：
[1] Univ British Columbia, Dept Biochem & Mol Biol, Mol Epigenet Grp, LSI, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada
来源：
FEBS LETTERS | 2011年 / 585卷 / 22期
关键词：
HIV-1; Latency; Chaetocin; SUV39H1; HDAC inhibitor; LONG TERMINAL REPEAT; IN-VIVO; TRANSCRIPTION FACTOR; REGULATES INDUCTION; TFII-I; EXPRESSION; LATENCY; ACTIVATION; CHROMATIN; PROMOTER;
D O I：
10.1016/j.febslet.2011.10.018
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：3549 / 3554
页数：6
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