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The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV‐1 without producing a T cell response
Author(s) -
Bernhard Wendy,
Barreto Kris,
Saunders Amy,
Dahabieh Matthew S.,
Johnson Pauline,
Sadowski Ivan
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.10.018
Subject(s) - acetylation , histone h3 , methyltransferase , provirus , chemistry , histone , histone deacetylase inhibitor , histone deacetylase , chromatin remodeling , microbiology and biotechnology , cancer research , biology , biochemistry , dna , methylation , genome , gene
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.