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

  作者 Bernhard, W; Barreto, K; Saunders, A; Dahabieh, MS; Johnson, P; Sadowski, I  
  选自 期刊  FEBS Letters;  卷期  2011年585-22;  页码  3549-3554  
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[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.

 
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