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Histone deacetylase inhibitors and HIV latency

Margolis, David M

Current Opinion in HIV & AIDS: January 2011 - Volume 6 - Issue 1 - p 25–29
doi: 10.1097/COH.0b013e328341242d
HIV reservoirs: from pathogenesis to drug development: Edited by Robert F. Siliciano and Janet D. Siliciano

Purpose of review: Interest has re-emerged in approaches to eradicate HIV infection. A series of modifications of nucleosomal histones within chromatin are a key mechanism of HIV gene regulation that alters the recruitment of transcription factors to viral DNA. The balance of these histone modifications in the vicinity of the HIV LTR plays an important role in the maintenance of proviral quiescence in rare latently infected cells, and presents a target for therapies aimed at purging this reservoir of persistent HIV infection.

Recent findings: Altering the balance of acetylase and deacetylase activity within CD4+ lymphocytes using histone deacetylase (HDAC) inhibitors, or other epigenetic drugs, has recently emerged as a promising approach to purge the reservoir of persistent infection. Multiple molecular mechanisms appear to underlie the establishment and maintenance of persistent, latent HIV infection, most frequently in the resting central memory CD4+ T cell. HDAC inhibitors perturb this balance, induce expression of integrated provirus, and may allow attack of this primary form of persistent HIV infection.

Summary: Although HDAC inhibitors are a promising approach, a better understanding of relevant mechanisms of latency in vivo, and better tools to translate this knowledge into therapies are needed.

Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Correspondence to David M. Margolis, MD, FACP, University of North Carolina at Chapel Hill, 2060 Genetic Medicine Bldg, CB#7042 Chapel Hill, NC 27599-7042, USA Tel: +1 919 966 6388; fax: +1 919 843 9976; e-mail: dmargo@med.unc.edu

© 2011 Lippincott Williams & Wilkins, Inc.