期刊
FEBS LETTERS
卷 585, 期 22, 页码 3549-3554出版社
WILEY
DOI: 10.1016/j.febslet.2011.10.018
关键词
HIV-1; Latency; Chaetocin; SUV39H1; HDAC inhibitor
资金
- Canadian Institutes for Health Research [MOP-77807, MOP-77712, CGD-96495]
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.
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