Document Detail


Targeting the JMJD2 Histone Demethylases to Epigenetically Control Herpesvirus Infection and Reactivation from Latency.
MedLine Citation:
PMID:  23303604     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Chromatin and the chromatin modulation machinery not only provide a regulatory matrix for enabling cellular functions such as DNA replication and transcription but also regulate the infectious cycles of many DNA viruses. Elucidation of the components and mechanisms involved in this regulation is providing targets for the development of new antiviral therapies. Initiation of infection by herpes simplex virus (HSV) requires the activity of several cellular chromatin modification enzymes including the histone demethylases LSD1 and the family of JMJD2 proteins that promote transcriptional activation of the initial set of viral genes. Depletion of the JMJD2 members or inhibition of their activity with a new drug results in repression of expression of viral immediate early genes and abrogation of infection. This inhibitor also represses the reactivation of HSV from the latent state in sensory neurons. Like HSV, the β-herpesvirus human cytomegalovirus also requires the activity of LSD1 and the JMJD2s to initiate infection, thus demonstrating the potential of this chromatin-based inhibitor to be useful against a variety of different viruses.
Authors:
Yu Liang; Jodi L Vogel; Jesse H Arbuckle; Ganesha Rai; Ajit Jadhav; Anton Simeonov; David J Maloney; Thomas M Kristie
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Science translational medicine     Volume:  5     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  167ra5     Citation Subset:  IM    
Affiliation:
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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