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

Wendy Bernhard; Kris Barreto; Amy Saunders; Matthew S. Dahabieh; Pauline Johnson; Ivan Sadowski

doi:10.1016/j.febslet.2011.10.018

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

Wendy Bernhard, Kris Barreto, Amy Saunders, Matthew S. Dahabieh, Pauline Johnson, Ivan Sadowski

Research output: Contribution to journal › Article › peer-review

Abstract

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. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	3549-3554
Number of pages	5
Journal	FEBS Letters
Volume	585
Issue number	22
DOIs	https://doi.org/10.1016/j.febslet.2011.10.018
Publication status	Published - 16 Nov 2011

Keywords

Chaetocin
HDAC inhibitor
HIV-1
Latency
SUV39H1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2011.10.018

Cite this

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

abstract = "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. {\textcopyright} 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.",

keywords = "Chaetocin, HDAC inhibitor, HIV-1, Latency, SUV39H1",

author = "Wendy Bernhard and Kris Barreto and Amy Saunders and Dahabieh, {Matthew S.} and Pauline Johnson and Ivan Sadowski",

year = "2011",

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doi = "10.1016/j.febslet.2011.10.018",

language = "English",

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journal = "FEBS Letters",

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TY - JOUR

T1 - The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response

AU - Bernhard, Wendy

AU - Barreto, Kris

AU - Saunders, Amy

AU - Dahabieh, Matthew S.

AU - Johnson, Pauline

AU - Sadowski, Ivan

PY - 2011/11/16

Y1 - 2011/11/16

N2 - 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. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

AB - 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. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

KW - Chaetocin

KW - HDAC inhibitor

KW - HIV-1

KW - Latency

KW - SUV39H1

U2 - 10.1016/j.febslet.2011.10.018

DO - 10.1016/j.febslet.2011.10.018

M3 - Article

VL - 585

SP - 3549

EP - 3554

JO - FEBS Letters

JF - FEBS Letters

IS - 22

ER -

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

Abstract

Keywords

UN SDGs

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