کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2048710 | 1074093 | 2011 | 6 صفحه PDF | دانلود رایگان |
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.
► Chaetocin, an inhibitor of the Suv39H1 methyltransferase, causes induction of latent HIV-1.
► Treatment with chaetocin does not cause a global T cell response.
► Chaetocin produces minimal toxicity at concentrations necessary for peak induction.
► HDAC inhibitors in combination with chaetocin cause a synergistic response of HIV-1 expression.
Journal: FEBS Letters - Volume 585, Issue 22, 16 November 2011, Pages 3549–3554