Inhibition of H3K27me3-specific histone demethylases JMJD3 and UTX blocks reactivation of herpes simplex virus 1 in trigeminal ganglion neurons

• Published in: Journal of virology 2015-03, Vol.89 (6), p.3417-3420
• Main Authors: Messer, Harald G P, Jacobs, Derek, Dhummakupt, Adit, Bloom, David C
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Animals; Down-Regulation - drug effects; Enzyme Inhibitors - pharmacology; Genome and Regulation of Viral Gene Expression; Herpes Simplex - enzymology; Herpes Simplex - genetics; Herpes Simplex - metabolism; Herpes Simplex - virology; Herpes simplex virus 1; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - physiology; Histone Demethylases - antagonists & inhibitors; Histone Demethylases - genetics; Histone Demethylases - metabolism; Histones - chemistry; Histones - genetics; Histones - metabolism; Humans; Jumonji Domain-Containing Histone Demethylases - antagonists & inhibitors; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Methylation; Mice; Neurons - enzymology; Neurons - metabolism; Neurons - virology; Trigeminal Ganglion - enzymology; Trigeminal Ganglion - metabolism; Trigeminal Ganglion - virology; Virus Activation - drug effects; Virus Latency - drug effects
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.03052-14

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.