Abstract
Herpes simplex virus 1 (HSV-1) genomes are associated with the repressive heterochromatic marks H3K9me2/me3 and H3K27me3 during latency. Previous studies have demonstrated that inhibitors of H3K9me2/me3 histone demethylases reduce the ability of HSV-1 to reactivate from latency. Here we demonstrate that GSK-J4, a specific inhibitor of the H3K27me3 histone demethylases UTX and JMJD3, inhibits HSV-1 reactivation from sensory neurons in vitro. These results indicate that removal of the H3K27me3 mark plays a key role in HSV-1 reactivation.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Motifs
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Animals
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Down-Regulation / drug effects
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Enzyme Inhibitors / pharmacology
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Herpes Simplex / enzymology*
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Herpes Simplex / genetics
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Herpes Simplex / metabolism
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Herpes Simplex / virology
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Herpesvirus 1, Human / drug effects
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Herpesvirus 1, Human / genetics
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Herpesvirus 1, Human / physiology*
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Histone Demethylases / antagonists & inhibitors
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Histone Demethylases / genetics
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Histone Demethylases / metabolism*
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Histones / chemistry
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Histones / genetics
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Histones / metabolism*
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Humans
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Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
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Jumonji Domain-Containing Histone Demethylases / genetics
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Jumonji Domain-Containing Histone Demethylases / metabolism*
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Methylation
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Mice
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Neurons / enzymology
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Neurons / metabolism*
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Neurons / virology
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Trigeminal Ganglion / enzymology
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Trigeminal Ganglion / metabolism*
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Trigeminal Ganglion / virology
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Virus Activation* / drug effects
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Virus Latency / drug effects
Substances
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Enzyme Inhibitors
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Histones
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Histone Demethylases
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Jumonji Domain-Containing Histone Demethylases
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Utx protein, mouse
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Kdm6b protein, mouse